Tagged: Biology Toggle Comment Threads | Keyboard Shortcuts

  • richardmitnick 3:29 pm on May 25, 2017 Permalink | Reply
    Tags: , Biology, , , Fertilizer research, Nitrogen fixation   

    From Caltech: “Nitrogen Fixation Research Could Shed Light on Biological Mystery” 

    Caltech Logo

    Caltech

    05/25/2017

    Emily Velasco
    626-395-6487
    evelasco@caltech.edu

    1
    Fertilizer is applied to an agricultural field. Credit: Credit: SoilScience.info (CC BY 2.0)

    New Process Could Make Fertilizer Production More Sustainable

    Inspired by a natural process found in certain bacteria, a team of Caltech researchers is inching closer to a new method for producing fertilizer that could some day hold benefits for farmers—particularly in the developing world—while also shedding light on a biological mystery.

    Fertilizers are chemical sources of nutrients that are otherwise lacking in soil. Most commonly, fertilizers supply the element nitrogen, which is essential for all living things, as it is a fundamental building block of DNA, RNA, and proteins. Nitrogen gas is very abundant on Earth, making up 78 percent of our atmosphere. However, most organisms cannot use nitrogen in its gaseous form.

    To make nitrogen usable, it must be “fixed”—turned into a form that can enter the food chain as a nutrient. There are two primary ways that can happen, one natural and one synthetic.

    Nitrogen fixation occurs naturally due to the action of microbes that live in nodules on plant roots. These organisms convert nitrogen into ammonia through specialized enzymes called nitrogenases. The ammonia these nitrogen-fixing organisms create fertilizes plants that can then be consumed by animals, including humans. In a 2008 paper appearing in the journal Nature Geoscience, a team of researchers estimated that naturally fixed nitrogen provides food for roughly half of the people living on the planet.

    The other half of the world’s food supply is sustained through artificial nitrogen fixation and the primary method for doing this is the Haber-Bosch process, an industrial-scale reaction developed in Germany over 100 years ago. In the process, hydrogen and nitrogen gases are combined in large reaction vessels, under intense pressure and heat in the presence of a solid-state iron catalyst, to form ammonia.

    “The gases are pressurized up to many hundreds of atmospheres and heated up to several hundred degrees Celsius,” says Caltech’s Ben Matson, a graduate student in the lab of Jonas C. Peters, Bren Professor of Chemistry and director of the Resnick Sustainability Institute. ” With the iron catalyst used in the industrial process, these extreme conditions are required to produce ammonia at suitable rates.”

    In a recent paper appearing in ACS Central Science, Matson, Peters, and their colleagues describe a new way of fixing nitrogen that’s inspired by how microbes do it.

    Nitrogenases consist of seven iron atoms surrounded by a protein skeleton. The structure of one of these nitrogenase enzymes was first solved by Caltech’s Douglas Rees, the Roscoe Gilkey Dickinson Professor of Chemistry. The researchers in Peters’ lab have developed something similar to a bacterial nitrogenase, albeit much simpler—a molecular scaffolding that surrounds a single iron atom.

    The molecular scaffolding was first developed in 2013 and, although the initial design showed promise in fixing nitrogen, it was unstable and inefficient. The researchers have improved its efficiency and stability by tweaking the chemical bath in which the fixation reaction occurs, and by chilling it to approximately the temperature of dry ice (-78 degrees Celsius). Under these conditions, the reaction converts 72 percent of starting material into ammonia, a big improvement over the initial method, which only converted 40 percent of the starting material into ammonia and required more energy input to do so.

    Matson, Peters, and colleagues say their work holds the potential for two major benefits:

    • Ease of production: Because the technology being developed does not require high temperatures or pressures, there is no need for the large-scale industrial infrastructure required for the Haber-Bosch process. This means it might some day be possible to fix nitrogen in smaller facilities located closer to where crops are grown.

    “Our work could help to inspire new technologies for fertilizer production,” says Trevor del Castillo, a Caltech graduate student and co-author of the paper. “While this type of a technology is unlikely to displace the Haber-Bosch process in the foreseeable future, it could be highly impactful in places that that don’t have a very stable energy grid, but have access to abundant renewable energy, such as the developing world. There’s definitely room for new technology development here, some sort of ‘on demand’ solar-, hydroelectric-, or wind-powered process.”

    • Understanding natural nitrogen fixation: The nitrogenase enzyme is complicated and finicky, not working if the ambient conditions are not right, which makes it difficult to study. The new catalyst, on the other hand, is relatively simple. The team believes that their catalyst is performing fixation in a conceptually similar way as the enzyme, and that its relative simplicity will make it possible to study fixation reactions in the lab using modern spectroscopic techniques.

    “One fascinating thing is that we really don’t know, on a molecular level, how the nitrogenase enzyme in these bacteria actually turns nitrogen into ammonia. It’s a large unanswered question,” says graduate student Matthew Chalkley, also a co-author on the paper.

    Peters says their research into this catalyst has already given them a deeper understanding of what is happening during a nitrogen-fixing reaction.

    “An advantage of our synthetic iron nitrogenase system is that we can study it in great detail,” he says. “Indeed, in addition to significantly improving the efficiency of this new catalyst for nitrogen fixation, we have made great progress in understanding, at the atomic level, the critical bond-breaking and making-steps that lead to ammonia synthesis from nitrogen.”

    If processes of this type can be further refined and their efficiency increased, Peters adds, they may have applications outside of fertilizer production as well.

    “If this can be achieved, distributed solar-powered ammonia synthesis can become a reality. And not just as a fertilizer source, but also as an alternative, sustainable, and storable chemical fuel,” he says.

    See the full article here .

    Please help promote STEM in your local schools.

    STEM Icon

    Stem Education Coalition

    The California Institute of Technology (commonly referred to as Caltech) is a private research university located in Pasadena, California, United States. Caltech has six academic divisions with strong emphases on science and engineering. Its 124-acre (50 ha) primary campus is located approximately 11 mi (18 km) northeast of downtown Los Angeles. “The mission of the California Institute of Technology is to expand human knowledge and benefit society through research integrated with education. We investigate the most challenging, fundamental problems in science and technology in a singularly collegial, interdisciplinary atmosphere, while educating outstanding students to become creative members of society.”

    Caltech campus

     
  • richardmitnick 10:49 am on May 25, 2017 Permalink | Reply
    Tags: , , , Biology, , Education: Combine and conquer, , ,   

    From Nature- “Education: Combine and conquer” 

    Nature Mag
    Nature

    25 May 2017
    Amber Dance

    1
    Nature

    Completing two graduate degrees can offer great flexibility.

    In 2009, veterinary ophthalmologist Ron Ofri took a call about a flock of sheep in northern Israel. Some of the lambs were day-blind: they wandered easily at night, but stood motionless when the Sun rose.

    Ofri, a researcher at the Hebrew University of Jerusalem who has a PhD and a doctorate in veterinary medicine (DVM), examined the sheep. Then he swapped his clinician’s hat for his research one, assessing the sheep’s retinal function and genome using techniques that he had learnt in graduate school. He and his colleagues then determined that some sheep carry a mutation in the same gene that causes human day-blindness. They successfully tested a gene therapy in sheep, and expect to soon launch human trials.

    The combination of a clinical and a research focus has been enormously beneficial, Ofri says. “One enriches the other.”

    Ofri is one of a small group of PhD scientists who have augmented their research training with a professional degree or a master’s in another topic — public health, for example, or physical therapy (see ‘Mix and match’). Data from the US National Science Foundation show that fewer than 1% of the 261,581 people who were awarded a PhD between 2011 and 2015 also earned a Doctor of Medicine (MD) degree. Even fewer combined a PhD with a dental degree.

    Obtaining multiple advanced degrees can open career doors and position scientists to act as a bridge between two fields of expertise. A downside, however, is that they can take a long time to complete — seven years or more, in some cases. The degrees are usually done sequentially, but some programmes make it possible to do them concurrently. The costs vary: during a PhD, tuition and stipends are usually covered by an adviser’s grant or other sources.

    But for professional degrees, students tend to pay their own way or have to apply for partial or full fellowships. Combination programmes can help to lower the costs, because they may fully or partially subsidize the clinical training. Furthermore, government schemes will often waive the repayment of loans for those who go on to perform clinical research.

    Whatever the route, people who successfully complete multiple advanced degrees tend to have clear goals for how they will apply the skills from each, and have the ability to rapidly switch back and forth between the two roles, as Ofri did in his sheep project.

    But it’s not the right course for everyone, says Tim Church, chief medical officer at ACAP Health, a consultancy firm in Dallas, Texas, who has an MD and a PhD. Those mulling over this route, he says, should carefully consider their interest in research and whether the dual degree will lead to a better job. The degrees ended up being a great choice for him, but the cost may not be worth the sacrifices for everyone.

    Bridge builders

    For many, the clinical component comes first. In Europe, for example, people wanting to become dentists generally spend five or six years in training directly after finishing secondary school, says Paulo Melo, a PhD dentist at the University of Porto in Portugal and chair of the working group on education and professional qualifications at the Council of European Dentists. They can then train in a speciality such as oral surgery, or pursue a research master’s or PhD. The number of people who go on to do the research component varies widely by nation and research field, he says.

    Liz Kay, founding dean of the Peninsula Dental School at Plymouth University, UK, has earned a clinical degree in dentistry, a Master of Public Health (MPH) and a PhD in clinical decision-making. Now, she runs a master’s of business administration programme for health-care workers. She spends one day a week in the clinic and teaches, researches and writes. “I’ve always tried to wedge open all my options,” Kay says.

    In the United States, dentistry students typically cannot enrol for a clinical degree, such as a Doctor of Dental Surgery (DDS), until they have done an undergraduate degree. And some universities offer the professional degrees together with a PhD.

    Box 1: Mix and match

    Degrees that can enhance a PhD include, but are not limited to, these programmes.

    MD A Doctor of Medicine often leads to work in academia, with most hours devoted to research, and some to clinical care.
    MBA A Master of Business Administration can help scientists to turn their research into start-up companies or to ascend in industry (see Nature 533, 569–570; 2016).
    JD A Juris Doctor degree allows scientists to apply their technical expertise in patent law (see Nature 423 666–667; 2003).
    DVM Graduates with a Doctor of Veterinary Medicine can perform translational research in academia and are highly sought after by pharmaceutical companies.
    DDS Many PhD graduates who have a Doctor of Dental Surgery stay in academia, teaching and performing research.
    MPH A Master of Public Health teaches rigorous statistics that enable researchers to work in areas such as epidemiology.
    DPT A Doctor of Physical Therapy helps PhD graduates to work in an academic post and to do research that informs clinical practice.
    PharmD A Doctor of Pharmacy with a PhD could work at a university or contribute to research or drug development in industry.
    DNP A Doctor of Nursing Practice prepares PhD graduates to perform research in nursing science and to teach in nursing schools.
    MSCI A Master of Science in Clinical Investigation produces a greater understanding of clinical research and opens up careers in clinical trials.
    MPP A Master of Public Policy sets graduates up to work in academia, government or research firms, analysing and developing child, family and educational policies.
    A.D.

    Professors who train students in such dual-degree programmes say that there’s a need for graduates who can change gear with ease. Michael Atchison, director of the veterinary–PhD programme at the University of Pennsylvania School of Veterinary Medicine in Philadelphia, says that his graduates are particularly desirable to pharmaceutical companies, which often struggle to find people who can adapt molecular and cellular data for use in an entire organism, he says.

    According to a 2013 report by the US National Academy of Sciences (NAS), about one-quarter of the veterinary surgeons in contract research organizations hold PhDs, and they work mostly in safety research. In animal-health companies, about one-third hold PhDs, and they work mainly in clinical research and development. According to a 2007 NAS questionnaire, 24 of 170, or 37%, of company job adverts for full-time vets sought candidates with a PhD and a veterinary degree.

    The NAS report estimated that an average of 83 North American vets enrolled in a PhD programme each year between 2007 and 2011. Further education is a popular option for vets in Europe. A 2015 survey by the Federation of Veterinarians of Europe found that 21% of veterinary-degree recipients earn a PhD or master’s as well.

    The dual degree may be a requirement for some jobs. Daisuke Ito says that applicants for his job as a medical-science liaison at Bristol-Myers Squibb in Fukuoka, Japan, were required to have both a PhD and an MD or veterinary-medicine degree. Liaisons use their scientific expertise throughout the drug-development process, and maintain relationships between the company and academic physicians.

    In 2014, Emory School of Medicine partnered up with the Georgia Institute of Technology in Atlanta to offer a combined PhD and doctor of physical therapy (DPT) scheme. They, too, expect that the graduates will fill a niche, not least because one-fifth of the US population has a disability, according to the US Centers for Disease Control and Prevention. “There’s a growing recognition about the need for robust rehabilitation science and researchers,” says programme director Edelle Field-Fote.

    Hiring committees may feel that having a PhD shows that a candidate has proven their ability to complete a complex project, says veterinary microbiologist Patrick Butaye of Ross University in Basseterre, West Indies. Butaye earned his veterinary degree at the University of Ghent in Belgium, where the six-year programme includes both undergraduate and graduate course work. He then got a PhD from the university, and now holds an associate appointment there.

    The system is similar in South Korea, says Jong Hyuk Kim, a cancer researcher at the University of Minnesota in Minneapolis. Kim wanted to know more about the diseases he’d been trained to treat during his six-year veterinary programme at Konkuk University in Seoul. So, in his final semester, he took some pathology courses that would count for credit in a PhD programme, and enrolled in that PhD course immediately after completing his veterinary degree. He estimates that about 10% of his classmates did so, too. Both Butaye and Kim note that their PhDs made it easier for them to find work abroad.

    Most countries allow people to work for two advanced degrees sequentially, but truly dual programmes seem to be concentrated in the United States. Yet even there, they are rare. About 120 US universities offer MD–PhD programmes, 15 have vet–PhD courses and around a dozen have PhD–DDS combinations.

    3
    Ron Ofri is often called on to assess eye infections at the Tisch Family Zoological Gardens in Jerusalem. Ron Ofri

    Dual programmes appeal most to students with a strong educational drive and clear goals. Osefame Ewaleifoh, for instance, was interested in combining tightly focused neurovirology questions with a wide view of public health. That brought him to the PhD–MPH programme at the Driskill Graduate Program in the Life Sciences at Northwestern University Feinberg School of Medicine in Chicago, Illinois. In his PhD lab, he studies the brain’s protections against viral invasion; in his public-health work, he’s implementing education for refugees to improve long-term health outcomes.

    Of course, joint programmes can be costly. At the University of Buffalo in New York, Erik Hefti is the first student to embark on a combined PhD–doctor of pharmacy course. He took out loans for his pharmacy degree. Now doing the PhD component, he works nights in a hospital pharmacy so that he can pay off those loans before they accumulate too much interest.

    For those who pay their own way through a professional course, the addition of a PhD can help to cut down on the debt. Church says that he owed nearly US$300,000 — mostly from the MD — by the time he’d finished medical school, a PhD and an MPH course. But because he went on to perform clinical research, government programmes helped Church to pay it off within ten years.

    Choose your adventure

    Even if a university doesn’t offer a specific dual programme, students may be able to design their own, says Steven Anderson, associate director for the Driskill programme, which now allows PhD students to pursue an MPH or a Master of Science in Clinical Investigation (MSCI), after a few students did so on their own.

    Eric Skaar was the first PhD student to do this. He was interested in molecular epidemiology, and hoped that the master’s would position him for jobs investigating disease outbreaks. At first, the university wasn’t eager to let him enrol in the MPH, which at the time was meant only for medical students. But by promising that it would enhance his PhD, not distract from it, he found faculty support.

    Skaar set rules with himself and his PhD adviser — that he’d be a research student until evening, when he attended his public-health classes. He aligned his two courses with a PhD dissertation on how the bacterium that causes gonorrhoea evades the immune system, and a public-health thesis on the epidemiology of the sexually transmitted infection. He never did become an outbreak investigator, but is now director of the division of molecular pathogenesis at Vanderbilt University School of Medicine in Nashville, Tennessee. Thanks to the MPH, he can approach his work on hospital infections with an epidemiological background.

    Students who want to create an ad hoc joint degree should be prepared to hack through plenty of bureaucratic red tape, warns Anderson. Particularly if the degrees are administered by different schools within an institution, basic issues such as tuition and class registration can be tricky. In fact, he’s not sure what form Driskill’s MPH option will take in the future, because he’s working out how to manage the tuition.

    Balancing act

    The multiple-degree path is mentally tricky, too. Ofri notes that people in his clinic don’t understand why he spends so much time in the lab, and his students wonder why he’s always in the clinic. It’s near-impossible to maintain a perfect 50–50 split, says Jaime Modiano, a graduate of the Penn vet–PhD course and now director of the Animal Cancer Care and Research Program at the University of Minnesota in Minneapolis and in St Paul. He decided to forego taking the veterinary board exam, opting for a research postdoc instead.

    Butaye made a similar decision: he researches antibiotic resistance in microbes. But he appreciates the veterinary degree for giving him the flexibility to work in multiple species.

    The balancing act is especially challenging for students during dual-degree programmes. “You have to be able to manage these two very different things you’re doing at the same time,” says Modiano.

    In veterinary classes, he had to memorize and integrate masses of information, then apply it immediately to treat animals. In research, he had to find the information himself and integrate it to spur future discoveries. “People who are successful are highly adaptable,” he says.

    See the full article here .

    Please help promote STEM in your local schools.

    STEM Icon

    Stem Education Coalition

    Nature is a weekly international journal publishing the finest peer-reviewed research in all fields of science and technology on the basis of its originality, importance, interdisciplinary interest, timeliness, accessibility, elegance and surprising conclusions. Nature also provides rapid, authoritative, insightful and arresting news and interpretation of topical and coming trends affecting science, scientists and the wider public.

     
  • richardmitnick 8:43 pm on May 21, 2017 Permalink | Reply
    Tags: , , Biology, , , , NanoFab, ,   

    From NIST: “Nanocollaboration Leads to Big Things” 

    NIST

    May 12, 2017 [Nothing like being timely getting into social media.]

    Ben Stein
    benjamin.stein@nist.gov
    (301) 975-2763

    1
    Entrance to NIST’s Advanced Measurement Laboratory in Gaithersburg, Maryland. Credit: Photo Courtesy HDR Architecture, Inc./Steve Hall Copyright Hedrich Blessing

    Roche Sequencing Solutions engineer Juraj Topolancik was looking for a way to decode DNA from cancer patients in a matter of minutes.

    Rajesh Krishnamurthy, a researcher with the startup company 3i Diagnostics, needed help in fabricating a key component of a device that rapidly identifies infection-causing bacteria.

    Ranbir Singh, an engineer with GeneSiC Semiconductor Inc., in Dulles, Virginia, sought to construct and analyze a semiconductor chip that transmits voltages large enough to power electric cars and spacecraft.

    These researchers all credit the NanoFab, located at the Center for Nanoscale Science and Technology (CNST) on the Gaithersburg, Maryland campus of the National Institute of Standards and Technology (NIST). The NanoFab provides cutting-edge nanotechnology capabilities for NIST scientists that is also accessible to outside users, with supplying the state-of-art tools, know-how and dependability to realize their goals.


    Learn more about the CNST NanoFab, where scientists from government, academia and industry can use commercial, state-of-the-art tools at economical rates, and get help from dedicated, full-time technical support staff. Voices: David Baldwin (Great Ball of Light, Inc.), Elisa Williams (Scientific & Biomedical Microsystems), George Coles (Johns Hopkins Applied Physics Laboratory) and William Osborn (NIST).

    When Krishnamurthy, whose company is based in Germantown, Maryland, needed an infrared filter for the bacteria-identifying chip, proximity was but one factor in reaching out to the NanoFab.

    “Even more important was the level of expertise you have here,” he says. “The attention to detail and the trust we have in the staff is so important—we didn’t have to worry if they would do a good job, which gives us tremendous peace of mind,” Krishnamurthy notes.

    The NanoFab also aided his project in another, unexpected way. Krishnamurthy had initially thought that the design for his company’s device would require a costly, highly customized silicon chip. But in reviewing design plans with engineers at the NanoFab, “they came up with a very creative way” to use a more standard, less expensive silicon wafer that would achieve the same goals, he notes.

    “The impact in the short term is that we didn’t have to pay as much [to build and test] the device at the NanoFab, which matters quite a bit because we’re a start-up company,” says Krishnamurthy. “In the long run, this will be a huge factor in [enabling us to mass produce] the device, keeping our costs low because, thanks to the input from the NanoFab, the source material is not a custom material.”

    Singh came to the NanoFab with a different mission. His company is developing a gallium nitride semiconductor device durable enough to transmit hundreds to thousands of volts without deteriorating. He relies on the NanoFab’s metal deposition tools and high-resolution lithography instruments to finish building and assess the properties of the device.

    2
    Semiconductor device, fabricated with the help of the NanoFab, designed to transmit high voltages.
    Credit: GeneSiC Semiconductor Inc.

    “Not only is there a wide diversity of tools, but within each task there are multiple technologies,” Singh adds.

    For instance, he notes, technologies offered at the NanoFab for depositing exquisitely thin and highly uniform layers of metal—which Singh found crucial for making reliable electrical contacts—include both evaporation and sputtering, he says.

    The wide range of metals available for deposition at the NanoFab, uncommon at other nanotech facilities, was another draw.

    “We needed different metals compared to those commonly used on silicon wafers and the NanoFab provided those materials,” notes Singh.

    Topolancik, the Roche Sequencing Solutions engineer, needed high precision etching and deposition tools to fabricate a device that may ultimately improve cancer treatment. His company‘s plan to rapidly sequence DNA from cancer patients could quickly determine if potential anti-cancer drugs and those already in use are producing the genetic mutations necessary to fight cancer.

    “We want to know if the drug is working, and if not, to stop using it and change the treatment,” says Topolancik.

    In the standard method to sequence the double-stranded DNA molecule, a strand is peeled off and resynthesized, base by base, with each base—cytosine, adenine, guanine and thymine—tagged with a different fluorescent label.

    “It’s a very accurate but slow method,” says Topolancik.

    Instead of peeling apart the molecule, Topolancik is devising a method to read DNA directly, a much faster process. Borrowing a technique from the magnetic recording industry, he sandwiches the DNA between two electrodes separated by a gap just nanometers in width.

    3

    Illustration of experiment to directly identify the base pairs of a DNA strand (denoted by A, C, T, G in graph). Tunneling current flows through DNA placed between two closely spaced electrodes. Different bases allow different amounts of current to flow, revealing the components of the DNA molecule.
    Credit: J. Topolancik/Roche Sequencing Solutions

    According to quantum theory, if the gap is small enough, electrons will spontaneously “tunnel” from one electrode to the other. In Topolancik’s setup, the tunneling electrons must pass through the DNA in order to reach the other electrode.

    The strength of the tunneling current identifies the bases of the DNA trapped between the electrodes. It’s an extremely rapid process, but for the technique to work reliably, the electrodes and the gap between them must be fabricated with extraordinarily high precision.

    That’s where the NanoFab comes in. To deposit layers of different metals just nanometers in thickness on a wafer, Topolancik relies on the NanoFab’s ion beam deposition tool. And to etch a pattern in those ultrathin, supersmooth layers without disturbing them—a final step in fabricating the electrodes—requires the NanoFab’s ion etching instrument.

    “These are specialty tools that are not usually accessible in academic facilities, but here [at the NanoFab] you have full, 24/7 access to them,” says Topolancik. “And if a tool goes down, it gets fixed right away,” he adds. “People here care about you, they want you to succeed because that’s the mission of the NanoFab.” As a result, he notes, “I can get done here in two weeks what would take half a year any place else.”


    Take a 360-degree walking tour of the CNST NanoFab in this video!

    See the full article here.

    Please help promote STEM in your local schools.

    STEM Icon

    Stem Education Coalition

    NIST Campus, Gaitherberg, MD, USA

    NIST Mission, Vision, Core Competencies, and Core Values

    NIST’s mission

    To promote U.S. innovation and industrial competitiveness by advancing measurement science, standards, and technology in ways that enhance economic security and improve our quality of life.
    NIST’s vision

    NIST will be the world’s leader in creating critical measurement solutions and promoting equitable standards. Our efforts stimulate innovation, foster industrial competitiveness, and improve the quality of life.
    NIST’s core competencies

    Measurement science
    Rigorous traceability
    Development and use of standards

    NIST’s core values

    NIST is an organization with strong values, reflected both in our history and our current work. NIST leadership and staff will uphold these values to ensure a high performing environment that is safe and respectful of all.

    Perseverance: We take the long view, planning the future with scientific knowledge and imagination to ensure continued impact and relevance for our stakeholders.
    Integrity: We are ethical, honest, independent, and provide an objective perspective.
    Inclusivity: We work collaboratively to harness the diversity of people and ideas, both inside and outside of NIST, to attain the best solutions to multidisciplinary challenges.
    Excellence: We apply rigor and critical thinking to achieve world-class results and continuous improvement in everything we do.

     
  • richardmitnick 3:32 pm on May 20, 2017 Permalink | Reply
    Tags: , , , Biology, Biology [et al] needs more staff scientists, , ,   

    From Nature: “Biology needs more staff scientists” 

    Nature Mag
    Nature

    16 May 2017
    Steven Hyman

    Independent professionals advance science in ways faculty-run labs cannot, and such positions keep talented people in research, argues Steven Hyman.

    1
    Staff scientist Stacey Gabriel co-authored 25 of the most highly cited papers worldwide in 2015. Maria Nemchuk/Broad Inst.

    [I have to ask, I do a Women in STEM series, why are the women I see always so good looking. This cannot be normal. No uglies, no fatties, that just does not compute.]

    Most research institutions are essentially collections of independent laboratories, each run by principal investigators who head a team of trainees. This scheme has ancient roots and a track record of success. But it is not the only way to do science. Indeed, for much of modern biomedical research, the traditional organization has become limiting.

    A different model is thriving at the Broad Institute of MIT and Harvard in Cambridge, Massachusetts, where I work.


    Broad Institute Campus

    In the 1990s, the Whitehead Institute for Biomedical Research, a self-governing organization in Cambridge affiliated with the Massachusetts Institute of Technology (MIT), became the academic leader in the Human Genome Project. This meant inventing and applying methods to generate highly accurate DNA sequences, characterize errors precisely and analyse the outpouring of data. These project types do not fit neatly into individual doctoral theses. Hence, the institute created a central role for staff scientists — individuals charged with accomplishing large, creative and ambitious projects, including inventing the means to do so. These non-faculty scientists work alongside faculty members and their teams in collaborative groups.

    When leaders from the Whitehead helped to launch the Broad Institute in 2004, they continued this model. Today, our work at the Broad would be unthinkable without professional staff scientists — biologists, chemists, data scientists, statisticians and engineers. These researchers are not pursuing a tenured academic post and do not supervise graduate students, but do cooperate on and lead projects that could not be accomplished by a single academic laboratory.

    Physics long ago saw the need to expand into different organizational models. The Manhattan Project, which during the Second World War harnessed nuclear energy for the atomic bomb, was not powered by graduate students. Europe’s particle-physics laboratory, CERN, does not operate as atomized labs with each investigator pursuing his or her own questions.

    LHC

    CERN/LHC Map

    CERN LHC Tunnel

    CERN LHC particles

    And the Jet Propulsion Laboratory at the California Institute of Technology in Pasadena relies on professional scientists to get spacecraft to Mars.


    NASA JPL-Caltech Campus

    A different tack

    In biology, many institutes in addition to the Broad are experimenting with new organizational principles. The Mechanobiology Institute in Singapore pushes its scientists to use tools from other disciplines by discouraging individual laboratories from owning expensive equipment unless it is shared by all. The Howard Hughes Medical Institute’s Janelia Research Campus in Ashburn, Virginia, the Salk Institute of Biological Sciences in La Jolla, California, and the Allen Institute for Brain Science in Seattle, Washington, effectively mix the work of faculty members and staff scientists. Disease-advocacy organizations, such as the ALS Therapy Development Institute in Cambridge, do their own research without any faculty members at all.

    Each of these institutes has a unique mandate, and many are fortunate in having deep resources. They also had to be willing to break with tradition and overcome cultural barriers.

    At famed research facilities of yore, such as Bell Labs and IBM Laboratories, the title ‘staff scientist’ was a badge of honour. Yet to some biologists the term suggests a permanent postdoc or senior technician — someone with no opportunities for advancement who works solely in a supervisor’s laboratory, or who runs a core facility providing straightforward services. That characterization sells short the potential of professional scientists.

    The approximately 430 staff scientists at the Broad Institute develop cutting-edge computational methods, invent and incorporate new processes into research pipelines and pilot and optimize methodologies. They also transform initial hits from drug screens into promising chemical compounds and advance techniques to analyse huge data sets. In summary, they chart the path to answering complex scientific questions.

    Although the work of staff scientists at the Broad Institute is sometimes covered by charging fees to its other labs, our faculty members would never just drop samples off with a billing code and wait for data to be delivered. Instead, they sit down with staff scientists to discuss whether there is an interesting collaboration to be had and to seek advice on project design. Indeed, staff scientists often initiate collaborations.

    Naturally, tensions still arise. They can play out in many ways, from concerns over how fees are structured, to questions about authorship. Resolving these requires effort, and it is a task that will never definitively be finished.

    In my view, however, the staff-scientist model is a win for all involved. Complex scientific projects advance more surely and swiftly, and faculty members can address questions that would otherwise be out of reach. This model empowers non-faculty scientists to make independent, creative contributions, such as pioneering new algorithms or advancing technologies. There is still much to do, however. We are working to ensure that staff scientists can continue to advance their careers, mentor others and help to guide the scientific direction of the institute.

    As the traditional barriers break down, science benefits. Technologies that originate in a faculty member’s lab sometimes attract more collaborations than one laboratory could sustain. Platforms run by staff scientists can incorporate, disseminate and advance these technologies to capture more of their potential. For example, the Broad Institute’s Genetic Perturbation Platform, run by physical chemist David Root, has honed high-throughput methods for RNA interference and CRISPR screens so that they can be used across the genome in diverse biological contexts. Staff scientists make the faculty more productive through expert support, creativity, added capacity and even mentoring in such matters as the best use of new technologies. The reverse is also true: faculty members help staff scientists to gain impact.

    Our staff scientists regularly win scientific prizes and are invited to give keynote lectures. They apply for grants as both collaborators and independent investigators, and publish regularly. Since 2011, staff scientists have led 36% of all the federal grants awarded for research projects at the Broad Institute (see ‘Staff-led grants’). One of our staff scientists, genomicist Stacey Gabriel, topped Thomson Reuters’ citation analysis of the World’s Most Influential Scientific Minds in 2016. She co-authored 25 of the most highly cited papers in 2015 — a fact that illustrates both how collaborative the Broad is and how central genome-analysis technologies are to answering key biological questions.

    3
    Source: Broad Inst.

    At the Broad Institute’s Stanley Center for Psychiatric Research, which I direct, staff scientists built and operate HAIL, a powerful open-source tool for analysis of massive genetics data sets. By decreasing computational time, HAIL has made many tasks 10 times faster, and some 100 times faster. Staff scientist Joshua Levin has developed and perfected RNA-sequencing methods used by many colleagues to analyse models of autism spectrum disorders and much else. Nick Patterson, a mathematician and computational biologist at the Stanley Center, began his career by cracking codes for the British government during the cold war. Today, he uses DNA to trace past migrations of entire civilizations, helps to solve difficult computational problems and is a highly valued support for many biologists.

    Irrational resistance

    Why haven’t more research institutions expanded the roles of staff scientists? One reason is that they can be hard to pay for, especially by conventional means. Some funding agencies look askance at supporting this class of professionals; after all, graduate students and postdocs are paid much less. In my years leading the US National Institute of Mental Health, I encountered people in funding bodies across the world who saw a rising ratio of staff to faculty members or of staff to students as evidence of fat in the system.

    That said, there are signs of flexibility. In 2015, the US National Cancer Institute began awarding ‘research specialist’ grants — a limited, tentative effort designed in part to provide opportunities for staff scientists. Sceptical funders should remember that trainees often take years to become productive. More importantly, institutions’ misuse of graduates and postdocs as cheap labour is coming under increasing criticism (see, for example, B. Alberts et al. Proc. Natl Acad. Sci. USA 111, 5773–5777; 2014).

    Faculty resistance is also a factor. I served as Harvard University’s provost (or chief academic officer) for a decade. Several years in, I launched discussions aimed at expanding roles for staff scientists. Several faculty members worried openly about competition for space and other scarce resources, especially if staff scientists were awarded grants but had no teaching responsibilities. Many recoiled from any trappings of corporatism or from changes that felt like an encroachment on their decision-making. Some were explicitly concerned about a loss of access and control, and were not aware of the degree to which staff scientists’ technological expertise and cross-disciplinary training could help to answer their research questions.

    Institutional leaders can mitigate these concerns by ensuring that staff positions match the shared goals of the faculty — for scientific output, education and training. They must explain how staff-scientist positions create synergies rather than silos. Above all, hiring plans must be developed collaboratively with faculty members, not by administrators alone.

    The Broad Institute attracts world-class scientists, as both faculty members and staff. Its appeal has much to do with how staff scientists enable access to advanced technology, and a collaborative culture that makes possible large-scale projects rarely found in academia. The Broad is unusual — all faculty members also have appointments at Harvard University, MIT or Harvard-affiliated hospitals. The institute has also benefited from generous philanthropy from individuals and foundations that share our values and believe in our scientific mission.

    Although traditional academic labs have been and continue to be very productive, research institutions should look critically and creatively at their staffing. Creating a structure like that of the Broad Institute would be challenging in a conventional university. Still, I believe any institution that is near an academic health centre or that has significant needs for advanced technology could benefit from and sustain the careers of staff scientists. If adopted judiciously, these positions would enable institutions to take on projects of unprecedented scope and scale. It would also create a much-needed set of highly rewarding jobs for the rising crop of talented researchers, particularly people who love science and technology but who do not want to pursue increasingly scarce faculty positions.

    A scientific organization should be moulded to the needs of science, rather than constrained by organizational traditions.

    See the full article here .

    Please help promote STEM in your local schools.

    STEM Icon

    Stem Education Coalition

    Nature is a weekly international journal publishing the finest peer-reviewed research in all fields of science and technology on the basis of its originality, importance, interdisciplinary interest, timeliness, accessibility, elegance and surprising conclusions. Nature also provides rapid, authoritative, insightful and arresting news and interpretation of topical and coming trends affecting science, scientists and the wider public.

     
  • richardmitnick 10:33 am on April 27, 2017 Permalink | Reply
    Tags: , , Biology, , Microbes Have Been Found Growing "Out of Nowhere" After a Volcanic Eruption,   

    From Science Alert: “Microbes Have Been Found Growing “Out of Nowhere” After a Volcanic Eruption” 

    ScienceAlert

    Science Alert

    26 APR 2017
    JACINTA BOWLER

    1
    George Burba/Shutterstock

    Life finds a way.

    When an underwater volcano erupts, completely altering the underwater landscape for kilometres, you’d assume it wouldn’t be the best place to look for new life.

    But researchers have discovered just that, identifying a new species of furry white bacteria covering a submerged volcano 130 metres (426 feet) below sea level in the Canary Islands.

    Even weirder – it appears to have started colonising the volcano as soon as the temperature dropped.

    “I bet there were microbes appearing there just as soon as those rocks got below 100 °C (212 °F),” says David Kirchman, from the University of Delaware, told Sam Wong at New Scientist.

    2
    Under the microscope: a single strand of Venus’s hair. Roberto Danovaro

    Back in 2011, the Canary Islands were hit by a number of tremors, while under water the Tagoro Volcano completely blanketed the seafloor with new rock over 138 days.

    Italian and Spanish researchers went to survey the area in 2014, expecting to see the underwater region still barren.

    Instead, they discovered that the volcano was covered in white, hair-like microbes – a species the researchers hadn’t seen before.

    “It was an impressive and surreal landscape, like discovering life on Mars,” Cinzia Corinaldesi, one of the researchers from the Polytechnic University of Marche told The Atlantic.

    3
    Satellite image of the discolored water (light blue) during the Tagoro volcano eruption in 2012. NASA Earth Observatory

    4
    CRG Marine Geosciences

    The white hair, which they’ve called Venus’s hair, was up to 3 centimetres (1 inch) long, and around 36-90 micrometres in diameter. (For reference, a human hair is between 17 and 180 micrometres in diameter.)

    And this wasn’t a small amount of fur – the researchers say it covered an area of roughly eight tennis courts (2,000 square metres, or about 21,500 square feet) across the volcano.

    But none of that answers how the hell it got there in the first place.

    “These organisms apparently come out of nowhere,” Kirchman told New Scientist.

    And not everything is as it appears, with countless passing microbes just waiting for an opportunity to settle and grow a family.

    “It’s helpful to remember that each drop of seawater contains millions of bacteria and that only one of them, in theory, is needed to colonise a new habitat, says Kirchman.

    “The Venus’s hair bacterium could have been in this ‘rare biosphere’ and by chance came across the virgin habitat created by the volcanic eruption.”

    Although the bacteria wouldn’t grow in the lab, the team sequenced its DNA, discovering that Venus’s hair was a completely new genus and species of the order Thiotrichales. The new scientific name for the hair is Thiolava veneris.

    Venus’s hair would have fed on the large amounts of hydrogen sulphide coming out of the rocks.

    While they’re only about 82 percent of the way through the DNA sequencing, the analysis does provide some hints on how Venus’s hair survives – it has a gene that produces a protein ‘pump’ capable of removing heavy metals that leach from the new volcanic rock.

    By the time the researchers had surveyed the area, the Venus’s hair was already acting as a welcoming committee – worms and crustaceans had started making the hair their home, reigniting life in that barren location.

    “A volcanic eruption is as devastating under the sea as it is on land, spewing out molten lava and toxic gas, destroying life in its shadow and disrupting habitats for kilometres in every direction,” writes Kirchman in a Nature editorial accompanying the piece.

    “But out of this destruction comes new land and the opportunity for life to begin again.”

    The research has been published in Nature Ecology & Evolution.

    See the full article here .

    Please help promote STEM in your local schools.

    STEM Icon

    Stem Education Coalition

     
  • richardmitnick 8:05 am on March 30, 2017 Permalink | Reply
    Tags: , Biology, , , , Ticks on the march   

    From NS: “Lyme disease is set to explode, and you can’t protect yourself” 

    NewScientist

    New Scientist

    29 March 2017
    Chelsea Whyte

    A new prediction says 2017 and 2018 will see major Lyme disease outbreaks in new areas. This could lead to lifelong health consequences, so where’s the vaccine?

    1
    Tick tock. Mike Peres/Custom Medical Stock Photo/SPL

    BY THE time he had finished his walk through the woods in New York state, Rick Ostfeld was ready to declare a public health emergency. He could read the warning signs in the acorns that littered the forest floor – seeds of a chain of events that will culminate in an unprecedented outbreak of Lyme disease this year.

    Since that day in 2015, Ostfeld has been publicising the coming outbreak. Thanks to a changing climate it could be one of the worst on record: the ticks that carry the disease have been found in places where it has never before been a problem – and where most people don’t know how to respond. The danger zone isn’t confined to the US: similar signs are flagging potential outbreaks in Europe. Polish researchers predict a major outbreak there in 2018.

    In theory, Ostfeld’s early warning system gives public health officials a two-year window to prepare. In many other cases, this would be enough time to roll out a vaccination programme. But there is no human vaccine for Lyme disease. Why not? And what can you do to protect yourself in the meantime?

    Lyme disease is the most common infection following an insect bite in the US: the Centers for Disease Control estimates that 300,000 Americans contract Lyme disease each year, calling it “a major US public health problem”. While it is easy enough to treat if caught early, we are still getting to grips with lifelong health problems that can stem from not catching it in time (see “Do I have Lyme disease?“).

    This is less of a problem when Lyme is confined to a few small areas of the US, but thanks in part to warmer winters, the disease is spreading beyond its usual territory, extending across the US (see map) and into Europe and forested areas of Asia. In Europe in particular, confirmed cases have been steadily rising for 30 years – today, the World Health Organization estimates that 65,000 people get Lyme disease each year in the region. In the UK, 2000 to 3000 cases are diagnosed each year, up tenfold from 2001, estimates the UK’s National Health Service.

    So how could a floor of acorns two years ago tell Ostfeld, a disease ecologist at the Cary Institute of Ecosystem Studies in Millbrook, New York, that 2017 would see an outbreak of Lyme disease? It’s all down to what happens next.

    A bumper crop of the seeds – “like you were walking on ball bearings” – comes along every two to five years in Millbrook. Crucially, these nutrient-packed meals swell the mouse population: “2016 was a real mouse plague of a year,” he says. And mouse plagues bring tick plagues.

    Soon after hatching, young ticks start “questing” – grasping onto grasses or leaves with their hind legs and waving their forelegs, ready to hitch a ride on whatever passes by, usually a mouse.

    Gut reaction

    Once on board, the feast begins. Just one mouse can carry hundreds of immature ticks in their post-larval nymph stage.

    This is where the problems for us start. Mouse blood carries the Lyme-causing bacterium Borrelia burgdorferi, which passes to a tick’s gut as it feeds. The tick itself is unharmed, but each time it latches onto a new host to feed, the bacteria can move from its gut to the blood – including that of any human passers-by.

    “We predict the mice population based on the acorns and we predict infected nymph ticks with the mice numbers. Each step has a one year lag,” Ostfeld says.

    Ostfeld published his discovery of this chain of causation in 2006 [PLOS Biology]. Last year, researchers in Poland found the same trend there, with the same implications. “Last year we had a lot of oak acorns, so we might expect 2018 will pose a high risk of Lyme,” says Jakub Szymkowiak at Adam Mickiewicz University in Poznan, Poland.

    Those who live in traditional Lyme disease zones are well versed in tick awareness – wear long trousers in the woods, check yourself thoroughly afterwards, and more. But this advice will be less familiar in places that used to sit outside Lyme zones – like Poland. “That’s sort of the perfect storm,” says Ostfeld. “The public is unaware, so they’re not looking for it and they don’t get treated.”

    It’s not obvious when you have been bitten or infected: ticks are the size of a poppy seed, and not everyone gets the classic “bullseye” rash that is supposed to tip you off. The flu-like symptoms that follow are also easy to misdiagnose. And because antibodies to Lyme disease take a few weeks to develop, early tests can miss it. “That’s when you get late-stage, untreated, supremely problematic Lyme disease,” Ostfeld says.

    The best approach would be to vaccinate people at risk – but there is currently no vaccine. We used to have one, but thanks to anti-vaccination activists, that is no longer the case.

    In the late 1990s, a race was on to make the first Lyme disease vaccine. By December 1998, the US Food and Drug Administration approved the release of Lymerix, developed by SmithKline Beecham, now GSK. But the company voluntarily withdrew the drug after only four years.

    This followed a series of lawsuits – including one where recipients claimed Lymerix caused chronic arthritis. Influenced by now-discredited research purporting to show a link between the MMR vaccine and autism, activists raised the question of whether the Lyme disease vaccine could cause arthritis.

    Media coverage and the anti-Lyme-vaccination groups gave a voice to those who believed their pain was due to the vaccine, and public support for the vaccine declined. “The chronic arthritis was not associated with Lyme,” says Stanley Plotkin, an adviser to pharmaceutical company Sanofi Pasteur. “When you’re dealing with adults, all kinds of things happen to them. They get arthritis, they get strokes, heart attacks. So unless you have a control group, you’re in la-la land.”

    But there was a control group – the rest of the US population. And when the FDA reviewed the vaccine’s adverse event reports in a retrospective study, they found only 905 reports for 1.4 million doses. Still, the damage was done, and the vaccine was benched.

    After that, “no one touched it”, says Thomas Lingelbach, CEO at Valneva, a biotech company based in France. Until now: Valneva has a vaccine in early human trials. It will improve on Lymerix, acting against all five strains of the disease instead of just the one most common in the US, and it will be suitable for children.

    Lingelbach knows the battles his firm will face. “It will be hard to convince anti-vax lobbyists,” he says. That fight is still some way off: any public roll-out is at least six years away.

    What makes this wait especially galling for some is that there is a vaccine for your pet. “It’s ironic that you can vaccinate your animal and you can’t vaccinate yourself,” Plotkin says.

    In the animal vaccine, instead of exposing Fido to a weakened version of the antigen to trigger antibodies, it works within the tick, neutralising B. burgdorferi by altering the expression of a protein on the bacterium before it enters the bloodstream. This is how a human version would work. “The underlying scientific principle is not very far away from what it is in the veterinary environment,” says Lingelbach.

    Some people have suggested taking the animal vaccine, but Plotkin doesn’t recommend this as it hasn’t been tested in people so there is insufficient safety data. “You just don’t have classical efficacy data in humans,” he says. It is also illegal in the US and UK for vets to practise medicine on humans.

    While we wait for a human vaccine, you might start keeping track of your local acorn populations – but brush up on your anti-tick measures before you hit the woods.

    See the full article here .

    Please help promote STEM in your local schools.

    STEM Icon

    Stem Education Coalition

     
    • stbarbebaker 4:50 pm on March 30, 2017 Permalink | Reply

      Reblogged this on stbarbebaker and commented:
      Here is an intriguing article about ticks and Lyme disease. Get your tea tree oil and diatomaceous earth now before Easter arrives, around about when the ticks begin to show up.

      Like

  • richardmitnick 11:05 am on March 24, 2017 Permalink | Reply
    Tags: , , Biology, , nicotinamide adenine dinucleotide (NAD+)   

    From COSMOS: “Can ageing be held at bay by injections and pills?” 

    Cosmos Magazine bloc

    COSMOS

    24 March 2017
    Elizabeth Finkel

    1
    Two fast ageing mice. The one on the left was treated with a FOXO4 peptide, which targets senescent cells and leads to hair regrowth in 10 days.
    Peter L.J. de Keizer

    The day we pop up a pill or get a jab to stave off ageing is closer, thanks to two high profile papers just published today.

    A Science paper from a team, led by David Sinclair from Harvard Medical School and the University of NSW, shows how popping a pill that raises the levels of a natural molecule called nicotinamide adenine dinucleotide (NAD+) staves off the DNA damage that leads to aging.

    The other paper, published in Cell, led by Peter de Keizer’s group at Erasmus University in the Netherlands, shows how a short course of injections to kill off defunct “senescent cells” reversed kidney damage, hair loss and muscle weakness in aged mice.

    Taken together, the two reports give a glimpse of how future medications might work together to forestall ageing when we are young, and delete damaged cells as we grow old. “This is what we in the field are planning”, says Sinclair.

    Sinclair has been searching for factors that might slow the clock of ageing for decades. His group stumbled upon the remarkable effects of NAD+ in the course of studying powerful anti-ageing molecules known as sirtuins, a family of seven proteins that mastermind a suite of anti-ageing mechanisms, including protecting DNA and proteins.

    Resveratrol, a compound found in red wine, stimulates their activity. But back in 2000, Sinclair’s then boss Lenny Guarente at MIT discovered a far more powerful activator of sirtuins – NAD+. It was a big surprise.

    “It would have to be the most boring molecule in the world”, notes Sinclair.

    It was regarded as so common and boring that no-one thought it could play a role in something as profound as tweaking the ageing clock. But Sinclair found that NAD+ levels decline with age.

    “By the time you’re 50, the levels are halved,” he notes.

    And in 2013, his group showed [Cell] that raising NAD+ levels in old mice restored the performance of their cellular power plants, mitochondria.

    One of the key findings of the Science paper is identifying the mechanism by which NAD+ improves the ability to repair DNA. It acts like a basketball defence, staying on the back of a troublesome protein called DBC1 to keep it away from the key player PARP1– a protein that repairs DNA.

    When NAD+ levels fall, DBC1 tackles PARP1. End result: DNA damage goes unrepaired and the cell ‘ages’.

    “We ‘ve discovered the reason why DNA repair declines as we get older. After 100 years that’s exciting,” says Sinclair .

    His group has helped developed a compound, nicotinamide mono nucleotide (NMN), that raises NAD+ levels. As reported in the Science paper, when injected into aged mice it restored the ability of their liver cells to repair DNA damage. In young mice that had been exposed to DNA-damaging radiation, it also boosted their ability to repair it. The effects were seen within a week of the injection.

    These kinds of results have impressed NASA. The organisation is looking for methods to protect its astronauts from radiation damage during their one-year trip to Mars. Last December it hosted a competition for the best method of preventing that damage. Out of 300 entries, Sinclair’s group won.

    As well as astronauts, children who have undergone radiation therapy for cancer might also benefit from this treatment. According to Sinclair, clinical trials for NMN should begin in six months. While many claims have been made for NAD+ to date, and compounds are being sold to raise its levels, this will be the first clinical trial, says Sinclair.

    By boosting rates of DNA repair, Sinclair’s drug holds the hope of slowing down the ageing process itself. The work from de Keizer’s lab, however, offers the hope of reversing age-related damage.

    His approach stems from exploring the role of senescent cells. Until 2001, these cells were not really on the radar of researchers who study ageing. They were considered part of a protective mechanism that mothballs damaged cells, preventing them from ever multiplying into cancer cells.

    The classic example of senescent cells is a mole. These pigmented skin cells have incurred DNA damage, usually triggering dangerous cancer-causing genes. To keep them out of action, the cells are shut down.

    If humans lived only the 50-year lifespan they were designed for, there’d be no problem. But because we exceed our use-by date, senescent cells end up doing harm.

    As Judith Campisi at the Buck Institute, California, showed in 2001, they secrete inflammatory factors that appear to age the tissues around them.

    But cells have another option. They can self-destruct in a process dubbed apoptosis. It’s quick and clean, and there are no nasty compounds to deal with.

    So what relegates some cells to one fate over another? That’s the question Peter de Keizer set out to solve when he did a post-doc in Campisi’s lab back in 2009.

    Finding the answer didn’t take all that long. A crucial protein called p53 was known to give the order for the coup de grace. But sometimes it showed clemency, relegating the cell to senesce instead.

    De Keizer used sensitive new techniques to identify that in senescent cells, it was a protein called FOXO4 that tackled p53, preventing it from giving the execution order.

    The solution was to interfere with this liaison. But it’s not easy to wedge proteins apart; not something that small diffusible molecules – the kind that make great drugs – can do.

    De Keizer, who admits to “being stubborn” was undaunted. He began developing a protein fragment that might act as a wedge. It resembled part of the normal FOXO4 protein, but instead of being built from normal L- amino acids it was built from D-amino acids. It proved to be a very powerful wedge.

    Meanwhile other researchers were beginning to show that executing senescent cells was indeed a powerful anti-ageing strategy. For instance, a group from the Mayo Clinic last year showed that mice genetically engineered to destroy 50-70% of their senescent cells in response to a drug experienced a greater “health span”.

    Compared to their peers they were more lively and showed less damage to their kidney and heart muscle. Their average lifespan was also boosted by 20%.

    But humans are not likely to undergo mass genetic engineering. To achieve similar benefits requires a drug that works on its own. Now de Keizer’s peptide looks like it could be the answer.

    As the paper in Cell shows, in aged mice, three injections of the peptide per week had dramatic effects. After three weeks, the aged balding mice regrew hair and showed improvements to kidney function. And while untreated aged mice could be left to flop onto the lab bench while the technician went for coffee, treated mice would scurry away.

    “It’s remarkable. it’s the best result I’ve seen in age reversal,” says Sinclair of his erstwhile competitor’s paper.

    Dollops of scepticism are healthy when it comes to claims of a fountain of youth – even de Keizer admits his work “sounds too good to be true”. Nevertheless some wary experts are impressed.

    “It raises my optimism that in our lifetime we will see treatments that can ameliorate multiple age-related diseases”, says Campisi.

    See the full article here .

    Please help promote STEM in your local schools.

    STEM Icon

    Stem Education Coalition

     
  • richardmitnick 10:53 am on March 24, 2017 Permalink | Reply
    Tags: , Biology, , Fight looms over evolution's essence, Palaeontologogy, Species selection   

    From COSMOS: “Macro or micro? Fight looms over evolution’s essence” 

    Cosmos Magazine bloc

    COSMOS

    24 March 2017
    Stephen Fleischfresser

    1
    Evolution over deep time: is it in the genes, or the species?
    Roger Harris/Science Photo Library

    A new paper threatens to pit palaeontologists against the rest of the biological community and promises to reignite the often-prickly debate over the question of the level at which selection operates.

    Carl Simpson, a researcher in palaeobiology at the Smithsonian Institution National Museum of Natural History, has revived the controversial idea of ‘species selection’: that selective forces in nature operate on whole species at a macroevolutionary scale, rather than on individuals at the microevolutionary level.

    Macroevolution, mostly concerned with extinct species, is the study of large-scale evolutionary phenomena across vast time spans. By contrast, microevolution focusses on evolution in individuals and species over shorter periods, and is the realm of biologists concerned with living organisms, sometimes called neontologists.

    Neontologists, overall, maintain that all evolutionary phenomena can be explained in microevolutionary terms. Macroevolutionists often disagree.

    In a paper, yet to be peer-reviewed, on the biological pre-print repository bioRxiv, Simpson has outlined a renewed case for species selection, using recent research and new insights, both scientific and philosophical. And this might be too much for the biological community to swallow.

    The debate over levels of selection dates to Charles Darwin himself and concerns the question of what the ‘unit of selection’ is in evolutionary biology.

    The default assumption is that the individual organism is the unit of selection. If individuals of a particular species possess a trait that gives them reproductive advantage over others, then these individuals will have more offspring.

    If this trait is heritable, the offspring too will reproduce at a higher rate than other members of the species. With time, this leads to the advantageous trait becoming species-typical.

    Here, selection is operating on individuals, and this percolates up to cause species-level characteristics.

    While Darwin favoured this model, he recognised that certain biological phenomena, such as the sterility of workers in eusocial insects such as bees and ants, could best be explained if selection operated at a group level.

    Since Darwin, scientists have posited different units of selection: genes, organelles, cells, colonies, groups and species among them.

    Simpson’s argument hinges on the kind of macroevolutionary phenomena common in palaeontology: speciation and extinction over deep-time. Species selection is real, he says, and is defined as, “a macroevolutionary analogue of natural selection, with species playing an analogous part akin to that played by organisms in microevolution”.

    Simpson takes issue with the argument that microevolutionary processes such as individual selection percolate up to cause macroevolutionary phenomena.

    He presents evidence contradicting the idea, and concludes that the “macroevolutionary patterns we actually observe are not simply the accumulation of microevolutionary change… macroevolution occurs by changes within a population of species.”

    How this paper will be received, only time will tell. A 2010 paper in Nature saw the famous evolutionary biologist E. O. Wilson recant decades of commitment to the gene as the unit of selection, hinting instead at group selection. The mere suggestion of this brought a sharp rebuke from 137 scientists.

    Simpson’s claim is more radical again, so we can only wait for the controversy to deepen.

    See the full article here .

    Please help promote STEM in your local schools.

    STEM Icon

    Stem Education Coalition

     
  • richardmitnick 10:14 am on March 16, 2017 Permalink | Reply
    Tags: , Biology, , , Deep-sea corals, Desmophyllum dianthus, , Study: Cold Climates and Ocean Carbon Sequestration, Why the earth goes through periodic climate change   

    From Caltech: “Study: Cold Climates and Ocean Carbon Sequestration” 

    Caltech Logo

    Caltech

    03/14/2017

    Robert Perkins
    (626) 395-1862
    rperkins@caltech.edu

    1
    Tony Wang (left) and Jess Adkins (right) with samples of Desmophyllum dianthus fossils.

    Deep-sea corals reveal why atmospheric carbon was reduced during colder time periods

    We know a lot about how carbon dioxide (CO2) levels can drive climate change, but how about the way that climate change can cause fluctuations in CO2 levels? New research from an international team of scientists reveals one of the mechanisms by which a colder climate was accompanied by depleted atmospheric CO2 during past ice ages.

    The overall goal of the work is to better understand how and why the earth goes through periodic climate change, which could shed light on how man-made factors could affect the global climate.

    Earth’s average temperature has naturally fluctuated by about 4 to 5 degrees Celsius over the course of the past million years as the planet has cycled in and out of glacial periods. During that time, the earth’s atmospheric CO2 levels have fluctuated between roughly 180 and 280 parts per million (ppm) every 100,000 years or so. (In recent years, man-made carbon emissions have boosted that concentration up to over 400 ppm.)

    About 10 years ago, researchers noticed a close correspondence between the fluctuations in CO2 levels and in temperature over the last million years. When the earth is at its coldest, the amount of CO2 in the atmosphere is also at its lowest. During the most recent ice age, which ended about 11,000 years ago, global temperatures were 5 degrees Celsius lower than they are today, and atmospheric CO2 concentrations were at 180 ppm.

    Using a library of more than 10,000 deep-sea corals collected by Caltech’s Jess Adkins, an international team of scientists has shown that periods of colder climates are associated with higher phytoplankton efficiency and a reduction in nutrients in the surface of the Southern Ocean (the ocean surrounding the Antarctic), which is related to an increase in carbon sequestration in the deep ocean. A paper about their research appears the week of March 13 in the online edition of the Proceedings of the National Academy of Sciences.

    “It is critical to understand why atmospheric CO2 concentration was lower during the ice ages. This will help us understand how the ocean will respond to ongoing anthropogenic CO2 emissions,” says Xingchen (Tony) Wang, lead author of the study. Wang was a graduate student at Princeton while conducting the research in the lab of Daniel Sigman, Dusenbury Professor of Geological and Geophysical Sciences. He is now a Simons Foundation Postdoctoral Fellow on the Origins of Life at Caltech.

    There is 60 times more carbon in the ocean than in the atmosphere—partly because the ocean is so big. The mass of the world’s oceans is roughly 270 times greater than that of the atmosphere. As such, the ocean is the greatest regulator of carbon in the atmosphere, acting as both a sink and a source for atmospheric CO2.

    Biological processes are the main driver of CO2 absorption from the atmosphere to the ocean. Just like photosynthesizing trees and plants on land, plankton at the surface of the sea turn CO2 into sugars that are eventually consumed by other creatures. As the sea creatures who consume those sugars—and the carbon they contain—die, they sink to the deep ocean, where the carbon is locked away from the atmosphere for a long time. This process is called the “biological pump.”

    A healthy population of phytoplankton helps lock away carbon from the atmosphere. In order to thrive, phytoplankton need nutrients—notably, nitrogen, phosphorus, and iron. In most parts of the modern ocean, phytoplankton deplete all of the available nutrients in the surface ocean, and the biological pump operates at maximum efficiency.

    However, in the modern Southern Ocean, there is a limited amount of iron—which means that there are not enough phytoplankton to fully consume the nitrogen and phosphorus in the surface waters. When there is less living biomass, there is also less that can die and sink to the bottom—which results in a decrease in carbon sequestration. The biological pump is not currently operating as efficiently as it theoretically could.

    To track the efficiency of the biological pump over the span of the past 40,000 years, Adkins and his colleagues collected more than 10,000 fossils of the coral Desmophyllum dianthus.

    Why coral? Two reasons: first, as it grows, coral accretes a skeleton around itself, precipitating calcium carbonate (CaCO3) and other trace elements (including nitrogen) out of the water around it. That process creates a rocky record of the chemistry of the ocean. Second, coral can be precisely dated using a combination of radiocarbon and uranium dating.

    “Finding a few centimeter-tall fossil corals 2,000 meters deep in the ocean is no trivial task,” says Adkins, Smits Family Professor of Geochemistry and Global Environmental Science at Caltech.

    Adkins and his colleagues collected coral from the relatively narrow (500-mile) gap known as the Drake Passage between South America and Antarctica (among other places). Because the Southern Ocean flows around Antarctica, all of its waters funnel through that gap—making the samples Adkins collected a robust record of the water throughout the Southern Ocean.

    Wang analyzed the ratios of two isotopes of nitrogen atoms in these corals – nitrogen-14 (14N, the most common variety of the atom, with seven protons and seven neutrons in its nucleus) and nitrogen-15 (15N, which has an extra neutron). When phytoplankton consume nitrogen, they prefer 14N to 15N. As a result, there is a correlation between the ratio of nitrogen isotopes in sinking organic matter (which the corals then eat as it falls to the seafloor) and how much nitrogen is being consumed in the surface ocean—and, by extension, the efficiency of the biological pump.

    A higher amount of 15N in the fossils indicates that the biological pump was operating more efficiently at that time. An analogy would be monitoring what a person eats in their home. If they are eating more of their less-liked foods, then one could assume that the amount of food in their pantry is running low.

    Indeed, Wang found that higher amounts of 15N were present in fossils corresponding to the last ice age, indicating that the biological pump was operating more efficiently during that time. As such, the evidence suggests that colder climates allow more biomass to grow in the surface Southern Ocean—likely because colder climates experience stronger winds, which can blow more iron into the Southern Ocean from the continents. That biomass consumes carbon, then dies and sinks, locking it away from the atmosphere.

    Adkins and his colleagues plan to continue probing the coral library for further details about the cycles of ocean chemistry changes over the past several hundred thousand years.

    The study is titled “Deep-sea coral evidence for lower Southern Ocean surface nitrate concentrations during the last ice age.” Coauthors include scientists from Caltech, Princeton University, Pomona College, the Max Planck Institute for Chemistry in Germany, University of Bristol, and ETH Zurich in Switzerland. This research was funded by the National Science Foundation, Princeton University, the European Research Council, and the Natural Environment Research Council.

    See the full article here .

    Please help promote STEM in your local schools.

    STEM Icon

    Stem Education Coalition

    The California Institute of Technology (commonly referred to as Caltech) is a private research university located in Pasadena, California, United States. Caltech has six academic divisions with strong emphases on science and engineering. Its 124-acre (50 ha) primary campus is located approximately 11 mi (18 km) northeast of downtown Los Angeles. “The mission of the California Institute of Technology is to expand human knowledge and benefit society through research integrated with education. We investigate the most challenging, fundamental problems in science and technology in a singularly collegial, interdisciplinary atmosphere, while educating outstanding students to become creative members of society.”
    Caltech buildings

     
  • richardmitnick 9:23 am on March 8, 2017 Permalink | Reply
    Tags: , Biology, , cure cancer, , , Push button,   

    From Paulson: Women in STEM – “Push button, cure cancer” Ph.D. candidates Nabiha Saklayen and Marinna Madrid 

    Harvard School of Engineering and Applied Sciences
    John A Paulson School of Engineering and Applied Sciences

    March 7, 2017
    Adam Zewe

    Two Harvard graduate students want to make curing blood cancer or HIV as easy as pressing a button.

    2
    Saklayen and Madrid are excited to move forward with their startup, Cellino. (Photo by Adam Zewe/SEAS Communications)

    1
    Cellino is a spinoff of the nanotechnology research being conducted in the Mazur lab. (Photo by Adam Zewe/SEAS Communications)

    Ph.D. candidates Nabiha Saklayen and Marinna Madrid have launched a startup to develop a simple, push-button device clinicians could use for gene therapy treatments. Their enterprise, Cellino, hopes to commercialize technology being developed in the lab of Eric Mazur, Balkanski Professor of Physics and Applied Physics at the John A. Paulson School of Engineering and Applied Sciences.

    The early-stage laboratory spinoff, which the pair launched in November, claimed first prize in the International Society for Optics and Photonics (SPIE) Startup Challenge, a pitch-off contest between more than 40 startups from around the world. In addition to winning $10,000 cash and $5,000 in optics products, Saklayen and Madrid were lauded for the impressive business potential of their startup.

    Their technique uses laser-activated nanostructures to deliver gene therapies directly into cells. When a laser is shined onto the nanostructures, the intense hot spots can open transient pores in nearby cells, Saklayen explained.

    “These pores are open long enough for any cargo that is around in the surrounding liquid to diffuse into the cell, and then the pores seal,” she said. “It is sort of like a magical opening where we can deliver molecules into the cell without damaging it, in a very targeted, quick way.”

    Developing effective intracellular delivery methods is a problem that has plagued biologists for decades, partly because the plasma membrane that surrounds a cell is selectively permeable and bars most molecules from entering.

    “Biologists have tried a number of different methods to do this, including viruses and chemical and physical processes, but none of them have been consistent enough and safe enough to be used reliably in treatments for blood disease,” said Madrid.

    The reliability of the nanostructure method developed at SEAS would give it a leg up over current practices. The biggest hurdle Madrid and Saklayen face now is translating the Mazur lab’s technology into a scalable, turnkey device.

    Their goal is to package the technology into a shoebox-sized device that contains everything a user needs—the laser, substrates, optical components, and computer interface. A user would put a patient’s cells and the nanofabricated chips into the device and use a touch screen to treat the cells, which could then be implanted into the patient.

    According to the Cellino team, those cells could be used to treat a number of different blood diseases, including HIV and blood cancers. By delivering gene-editing molecules into a patient’s hematopoietic stem cells, for instance, a clinician could repopulate a patient’s bone marrow with HIV-resistant cells. To treat cancers that affect the blood, the technology could be used to weaponize a patient’s T-cells, and then return them to the blood stream to attack the cancer.

    “What I find really exciting about this project is it is really pushing the barriers of what is the norm,” Saklayen said. “People talk about curing blood cancer all the time, but we have this unique opportunity to really enable that. That is the most inspiring part—we have an opportunity to make a difference in people’s lives. That is what drives me everyday to keep working hard.”

    As they move forward with Cellino, Saklayen and Madrid are working closely with Harvard’s Office of Technology Development (OTD), which has filed patent applications to secure the lab’s intellectual property and develop a viable commercialization strategy for the technology. Alan Gordon, a Director of Business Development in OTD, has been advising the team on how to develop a business plan and launch the company.

    After graduating from the Ph.D. program this spring, Saklayen will pursue Cellino full time. Madrid plans to graduate early so she can soon focus solely on the company, too. The co-founders have applied to a number of startup incubators and plan to enter additional pitch competitions to gain more validation for both their technology and their business plan.

    “There is definitely a production challenge when you talk about making things at a larger scale, but we are making good progress,” Madrid said. “The technology is very powerful because it is so streamlined. Now it is all about packaging.”

    Mazur is proud of his students’ accomplishments and excited for the potential of their startup. “This work is really transformative and opens the door to new therapies for currently incurable diseases,” he said.

    See the full article here .

    Please help promote STEM in your local schools.

    STEM Icon

    Stem Education Coalition

    Through research and scholarship, the Harvard School of Engineering and Applied Sciences (SEAS) will create collaborative bridges across Harvard and educate the next generation of global leaders. By harnessing the power of engineering and applied sciences we will address the greatest challenges facing our society.

    Specifically, that means that SEAS will provide to all Harvard College students an introduction to and familiarity with engineering and technology as this is essential knowledge in the 21st century.

    Moreover, our concentrators will be immersed in the liberal arts environment and be able to understand the societal context for their problem solving, capable of working seamlessly withothers, including those in the arts, the sciences, and the professional schools. They will focus on the fundamental engineering and applied science disciplines for the 21st century; as we will not teach legacy 20th century engineering disciplines.

    Instead, our curriculum will be rigorous but inviting to students, and be infused with active learning, interdisciplinary research, entrepreneurship and engineering design experiences. For our concentrators and graduate students, we will educate “T-shaped” individuals – with depth in one discipline but capable of working seamlessly with others, including arts, humanities, natural science and social science.

    To address current and future societal challenges, knowledge from fundamental science, art, and the humanities must all be linked through the application of engineering principles with the professions of law, medicine, public policy, design and business practice.

    In other words, solving important issues requires a multidisciplinary approach.

    With the combined strengths of SEAS, the Faculty of Arts and Sciences, and the professional schools, Harvard is ideally positioned to both broadly educate the next generation of leaders who understand the complexities of technology and society and to use its intellectual resources and innovative thinking to meet the challenges of the 21st century.

    Ultimately, we will provide to our graduates a rigorous quantitative liberal arts education that is an excellent launching point for any career and profession.

     
c
Compose new post
j
Next post/Next comment
k
Previous post/Previous comment
r
Reply
e
Edit
o
Show/Hide comments
t
Go to top
l
Go to login
h
Show/Hide help
shift + esc
Cancel
%d bloggers like this: