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  • richardmitnick 5:36 pm on July 11, 2017 Permalink | Reply
    Tags: , , Female astronomers of colour face daunting discrimination, NATURE, Not in this article but so do caucasion women esp in Physics and Astronomy   

    From Nature: “Female astronomers of colour face daunting discrimination” 

    Nature Mag
    Nature

    11 July 2017
    Rachael Lallensack

    Two-fifths report feeling unsafe at work, and 21% have concerns about attending conferences.

    Women of colour working in astronomy and planetary science experience high rates of harassment at work, a study finds. In a survey, a striking 40% of these scientists reported feeling unsafe in their workplaces owing to their gender, and 28% reported feeling unsafe on account of their race.

    The findings, published on 10 July in the Journal of Geophysical Research: Planets [1], illustrate a well-researched phenomenon: a woman’s risk of being subjected to gendered or race-based harassment is higher if she belongs to multiple minority groups. Women of colour were more likely than white women or men of colour to recall a negative workplace experience during a five-year period from 2011-2015. Such incidents included having their mental or physical ability questioned.

    “This is something that I’ve known about, that I’ve seen and experienced, as someone of colour, for as long as I’ve been in the field. So I’m not surprised,” says Cristina Thomas, an astronomer at the Planetary Science Institute who is based at NASA’s Goddard Space Flight Center in Greenbelt, Maryland. “I was very happy to see someone quantify what was happening so other people would see it.”

    The study, whose participants ranged from undergraduate students to senior researchers, suggests that the negative environment experienced by many female scientists of colour is often apparent to colleagues of other genders or ethnicities.

    Eighty-eight per cent of the 474 participants — a group that was 84% white and included both men and women — had heard remarks that were racist, sexist or directed at a person’s gender or intelligence in their current workplace.

    Survey respondents included 45 women of colour, who collectively accounted for 11% of participants. That proportion is double the percentage of minority women in the United States who hold bachelor’s degrees in physical science. [That is a sad statistic. In The U.S. we suck at acknowledging talent and we just lose it.]

    The analysis is the first of its kind in the astronomy and planetary-science fields, and one of few in a science, technology, engineering or medicine discipline that specifically examines the experiences of women of colour, says study co-author Christina Richey, former chair of the American Astronomical Society’s Committee on the Status of Women in Astronomy in Washington DC. The research team was made up of two planetary scientists and two social scientists, including anthropologist Kathryn Clancy of the University of Illinois at Urbana-Champaign, who led a high-profile survey of harassment in scientific fieldwork that was published in 2014 in PLoS ONE [2]

    The latest study found that harassment and discrimination can have a heavy impact on an individual’s career decisions. Twenty-one per cent of men of colour, 18% of women of colour and 12% of white women reported avoiding a class, conference or professional event because they did not feel safe attending. [Think of the talent lost.] Such events can help to foster professional networks, mentorship and opportunities for collaboration — connections that can advance a scientist’s career, says Zuleyka Zevallos, a sociologist at Swinburne University of Technology in Melbourne, Australia.

    Systemic solutions

    “If a culture of hostility remains in place, it doesn’t matter what we do at the individual level because the system is broken. The pipeline is broken,” says Zevallos, who helped to implement gender-education programmes at universities in her former position at the Australian Academy of Science in Canberra.

    The analysis has sparked intense discussion online among astronomers and planetary scientists. Several female scientists of colour have shared their stories on Twitter, describing the significant, but sometimes subtle, consequences of harassment and discrimination in their own lives.

    Chanda Prescod-Weinstein, a theoretical physicist at the University of Washington in Seattle, tweeted that when faced with events that she thought might expose her to harassment, discrimination or other negative experiences, she sometimes brought her husband along. But that created an extra financial burden for the couple.

    In recent years, professional societies such as the American Astronomical Society and American Geophysical Union have taken steps to prevent harassment at their meetings. The latest study suggests several actions that research institutions, funding agencies and scientific societies can take to reduce harassment. These include updating their codes of conduct to bar harassment; instituting mandatory cultural-awareness training; encouraging leading researchers to model appropriate behaviour; and putting in place swift sanctions for perpetrators.

    “It’s time to pivot away from the conversation of, ‘Is gender equity and racism a problem in science?’, and shift to taking action,” Zevallos says. “We can’t afford to lose more women of colour, white women and under-represented minorities.”

    [Think about it: if a back Jewish female lesbian magician pulled a rabbit out of a hat, no one would give a rat’s ass about her race, religion or sexual preference. She just pulled a rabbit out of a hat.]

    See the full article here .

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    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 10:12 am on July 5, 2017 Permalink | Reply
    Tags: , “...Full and continued engagement” with the United Kingdom in FP9 would be “an obvious win-win for the UK and the EU”, , European Research Council (ERC) which as part of H2020 was given a €13.1-billion budget to fund basic research for 2014–20, Europe’s next big science-funding programme urged to double its budget, FP9-Framework Programme Nine, , Less bureaucracy, NATURE, One-fifth of the number of fast-growing start-up firms that the United States does, Pascal Lamy, Science Europe, The region trails South Korea on business-research spending, Uncertainty over Brexit negotiations   

    From Nature: “Europe’s next big science-funding programme urged to double its budget” 

    Nature Mag
    Nature

    04 July 2017
    Alison Abbott

    1
    Pascal Lamy. Julien Warnand/EPA.

    Midway through the European Union’s sprawling 7-year, €75-billion (US$85-billion) research-funding programme known as Horizon 2020 (H2020), scientists are already angling for more money and less red tape in its successor.

    So researchers are delighted with an influential 3 July report that urges the EU to double the budget of its next funding scheme, called Framework Programme Nine (FP9), which is due to launch in 2021. The report says that FP9’s structure should be largely similar to that of H2020, but with less bureaucracy, and suggests that it includes a few major ‘moonshot’ missions in areas such as energy and information technology.

    “Scientists are generally happy with the report because it mostly confirms our thinking,” says Stephan Kuster, the acting director of Science Europe, a Brussels-based organization that represents member-state research agencies. But it lacks details on some of its aims, he says: in particular, how to persuade politicians to approve such a large budget hike.

    The report comes from a group of academic and industry experts invited by the European Commission to formulate a vision for future research plans, headed by a former director-general of the World Trade Organization, Pascal Lamy. Commission insiders say its ideas will strongly influence the shape of FP9 — set to be the first major EU funding programme to take place after the United Kingdom leaves the union in 2019.

    Uncertainty over Brexit negotiations means that the commission isn’t close to determining its total post-2020 budget, and it will not propose what FP9 might look like until the end of this year. That has not stopped advocates asking for more cash: in June, a research committee for the European Parliament proposed a €120-billion budget for FP9, assuming that, like H2020, it will run for 7 years.

    In an interview with the European Commission alongside his report, Lamy calls that “a bare minimum”. His team’s report says that whatever the result of Brexit negotiations, “full and continued engagement” with the United Kingdom in FP9 would be “an obvious win-win for the UK and the EU”. The programme should also be opened up more widely to non-EU countries, the report says.

    Falling success rates

    European scientists have a love–hate relationship with the EU’s massive research programmes. Researchers appreciate the funding and the support of collaborative projects, but deplore the bureaucracy and the way each new programme changes the rules. An interim evaluation of H2020, published in May, suggests it has been more popular than its predecessors, in part because of cuts to red tape.

    Still, the evaluation noted that H2020 is heavily oversubscribed, with barely 1 in 9 applications funded — well down on its predecessor programme, which funded nearly 1 in 5. FP9 should return to earlier levels, the Lamy report says.

    Success rates are even lower, below 1 in 10, at the prestigious European Research Council (ERC), which as part of H2020 was given a €13.1-billion budget to fund basic research for 2014–20. The ERC is supposed to reward excellence, but in some of its grant programmes, half of the projects deemed “excellent” by reviewers have gone unfunded. “We would need to double our budget to make sense of our mission,” says ERC president Jean-Pierre Bourguignon.

    The Lamy report recommends keeping H2020’s broad divisions into grants for excellent science, for industrial-innovation projects, and for multinational collaborations that meet societal grand challenges. It suggests that rules of participation be made simpler — with documentation and reporting obligations kept to a minimum, and audits restricted to cases where fraud is suspected. And it proposes that FP9 adopt broader measures of the ‘impact’ of work — going beyond scientific impact to capture effects on policymaking and industrial competitiveness, for instance.

    The EU has an ‘innovation gap’ compared with its trading partners, the report says, noting that the region trails South Korea on business-research spending, and has one-fifth of the number of fast-growing start-up firms that the United States does.

    The report also argues that FP9 should do more to involve Europe’s citizens, including involving them in choosing ‘moonshot’ missions in areas of societal importance, such as climate change, that set targets to be achieved within precise time frames. (As an example, it suggests producing carbon-free steel by 2030.)

    In general, scientists should get better at communicating their work using stories that citizens can understand, the report says: “Communicating on science should become part of researchers’ career and their reward system.”

    See the full article here .

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    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 1:15 pm on June 25, 2017 Permalink | Reply
    Tags: , , Bacteriophages, , Genetically modified viruses, NATURE   

    From Nature: “Modified viruses deliver death to antibiotic-resistant bacteria” 

    Nature Mag
    Nature

    21 June 2017
    Sara Reardon

    Engineered microbes turn a bacterium’s immune response against itself using CRISPR.

    1
    Phages (green) attack a bacterium (orange). Researchers are hoping to use engineered versions of these viruses to fight antibiotic resistance. AMI Images/SPL

    Genetically modified viruses that cause bacteria to kill themselves could be the next step in combating antibiotic-resistant infections [Nature].

    Several companies have engineered such viruses, called bacteriophages, to use the CRISPR gene-editing system to kill specific bacteria, according to a presentation at the CRISPR 2017 conference in Big Sky, Montana, last week. These companies could begin clinical trials of therapies as soon as next year.

    Initial tests have saved mice from antibiotic-resistant infections that would otherwise have killed them, said Rodolphe Barrangou, chief scientific officer of Locus Biosciences in Research Triangle Park, North Carolina, at the conference.

    Bacteriophages isolated and purified from the wild have long been used to treat infections in people, particularly in Eastern Europe. These viruses infect only specific species or strains of bacteria, so they have less of an impact on the human body’s natural microbial community, or microbiome, than antibiotics do. They are also generally thought to be very safe for use in people.

    But the development of phage therapy has been slow, in part because these viruses are naturally occurring and so cannot be patented. Bacteria can also quickly evolve resistance to natural phages, meaning researchers would have to constantly isolate new ones capable of defeating the same bacterial strain or species. And it would be difficult for regulatory agencies to continually approve each new treatment.

    CRISPR-fuelled death

    To avoid these issues, Locus and several other companies are developing phages that turn the bacterial immune system known as CRISPR against itself. In Locus’ phages, which target bacteria resistant to antibiotics, the CRISPR system includes DNA with instructions for modified guide RNAs that home in on part of an antibiotic-resistance gene. Once the phage infects a bacterium, the guide RNA latches on to the resistance gene. That prompts an enzyme called Cas3, which the bacterium normally produces to kill phages, to destroy that genetic sequence instead. Cas3 eventually destroys all the DNA, killing the bacterium. “I see some irony now in using phages to kill bacteria,” says Barrangou.

    Another company, Eligo Bioscience in Paris, uses a similar approach. It has removed all the genetic instructions that allow phages to replicate, and inserted DNA that encodes guide RNAs and the bacterial enzyme Cas9. Cas9 cuts the bacterium’s DNA at a designated spot, and the break triggers the bacterium to self-destruct. The system will target human gut pathogens, says Eligo chief executive Xavier Duportet, although he declined to specify which ones.

    The two companies hope to start clinical trials in 18–24 months. Their first goal is to treat bacterial infections that cause severe disease. But eventually, they want to develop phages that let them precisely engineer the human microbiome by removing naturally occurring bacteria associated with conditions such as obesity, autism and some cancers.

    Both Barrangou and Duportet acknowledge that for now, causal links between the human microbiome and these conditions are tenuous at best. But they hope that by the time their therapies have been proved safe and effective in humans, the links will be better understood. Phages could also allow researchers to manipulate the microbiomes of experimental animals, which could help them to untangle how certain bacteria influence conditions such as autism, says Timothy Lu, a synthetic biologist at the Massachusetts Institute of Technology in Cambridge and a co-founder of Eligo.

    An engineered solution

    Other companies are working to get phages to perform different tasks. ‘Supercharged’ phages, created by a group at Synthetic Genomics in La Jolla, California, could contain dozens of special features, including enzymes that break down biofilms or proteins that help to hide the phages from the human immune system.

    But engineered phages still have to overcome some hurdles. Treating an infection might require a large volume of phages, says Elizabeth Kutter, a microbiologist at Evergreen State College in Olympia, Washington, and it’s unclear whether this would trigger immune reactions, some of which could interfere with the treatment. Phages could also potentially transfer antibiotic-resistance genes to non-resistant bacteria, she notes.

    Lu adds that bacteria may still develop resistance even to the engineered phages. So researchers might have to frequently modify their phages to keep up with bacterial mutations.

    But as antibiotic resistance spreads, Kutter says, there will be plenty of space for both engineered phages and natural phage therapies, which are also growing in popularity. “I think they’ll complement the things that can be done by natural phages that have been engineered for hundreds of thousands of years,” she says.

    Related stories and links
    See the full article for further references with links

    See the full article here .

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    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 8:09 pm on June 2, 2017 Permalink | Reply
    Tags: , , , , NATURE   

    From Nature: “Next-generation cancer drugs boost immunotherapy responses” 

    Nature Mag
    Nature

    02 June 2017
    Heidi Ledford

    Early clinical trial data suggest that combining medicines improves treatment.

    1
    Combining cancer treatments can boost remission rates in patients with kidney cancer. David McCarthy/SPL

    An approach to unleashing immune responses against cancer is showing promise in early clinical trials, and may boost the effectiveness of existing therapies.

    The experimental drugs target a protein called IDO, which starves immune cells by breaking down the crucial amino acid tryptophan. IDO can suppress immune responses and rein in potentially damaging inflammation. But it can also halt the body’s natural immune response to cancer and allow tumours to grow unchecked. Some tumours even express IDO to shield themselves from the immune system.

    Researchers will present the latest round of clinical data from IDO-inhibiting drugs at the American Society of Clinical Oncology (ASCO) annual meeting in Chicago, Illinois, on 2–6 June. The results add to mounting evidence that IDO inhibitors boost the effectiveness of treatments called immunotherapies, which bolster immune responses against cancer. “It’s almost like you’re taking down a tumour force field,” says Michael Postow, a cancer researcher at the Memorial Sloan Kettering Cancer Center in New York City.

    One problem is that tumours express a host of proteins that shut down immune responses, so blocking PD-1 may simply allow another protein to step in. Researchers are frantically searching for ways to boost the success rates of PD-1 inhibitors by combining them with drugs that can block these other proteins. “There are ways around every single one of these checkpoint proteins,” says immunologist Andrew Mellor of Newcastle University, UK. “Therein lies the problem — and therein lies the solution.”

    Greater than the sum of its parts?

    Pharmaceutical companies have been racing to test the effectiveness of combining experimental IDO-inhibiting drugs with approved PD-1 inhibitors. NewLink Genetics in Ames, Iowa, announced in April that combining its IDO-pathway inhibitor indoximod with an anti-PD1 drug shrank tumours in 31 of 60 people with advanced melanoma in the trial.

    And data to be presented at the ASCO meeting suggest that an IDO inhibitor called epacadostat, made by Incyte of Wilmington, Delaware, could boost response rates to anti-PD-1 drugs in lung and kidney cancers. Thirty-five percent of people with non-small-cell lung cancer responded to the combination. In kidney cancer, the combination shrank tumours in 47% of trial participants.

    Other companies are also testing IDO inhibitors — including a firm co-founded by cancer researcher Benoit Van den Eynde of the Ludwig Institute for Cancer Research in Brussels. In 2003, Van den Eynde’s team became the first to demonstrate that IDO is expressed in human tumours1. His company, iTeos Therapeutics in Gosselies, Belgium, has partnered with the pharmaceutical giant Pfizer in New York City, and brought its IDO inhibitor into clinical trials last year.

    It is still early, cautions cancer immunologist Thomas Gajewski of the University of Chicago in Illinois, who has worked on clinical trials of IDO inhibitors. The trials so far have been small and lack a control group that received only PD-1 inhibitors. As a result, researchers can only compare the results of drug combinations with the historical success rates of PD1 inhibitors.

    And there is still a lot to learn about how IDO interacts with the immune system, or what effects an IDO inhibitor could have elsewhere in the body, says Michael Platten, an oncologist at the German Cancer Research Center in Heidelberg. IDO is expressed in many tissues. “This is still a relatively new field,” says Platten. “We do not really understand the molecular mechanism.”

    But an encouraging sign, adds Gajewski, is that so far, the combination of drugs to inhibit IDO and PD-1 seems to be relatively safe, and lacks the toxicity seen when PD-1 inhibitors are used with some other cancer drugs. “In some of the combinations, it looks like there’s benefit beyond anti-PD-1 alone, but without toxicity,” he says. “For me, that’s really an opportunity.”

    See the full article here .

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    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 12:42 pm on May 31, 2017 Permalink | Reply
    Tags: , , , , NATURE, Roque de los Muchachos in La Palma the Canary Islands - the back up site,   

    From Nature: “Canada weighs scientific consequences of moving a mega-telescope’ 

    Nature Mag
    Nature

    30 May 2017
    Alexandra Witze

    1
    Existing telescopes atop Mauna Kea take advantage of the mountain’s world-class astronomical observing conditions. Babak Tafreshi/NGC

    Is second-best good enough? That’s the question Canadian astronomers will confront this week as they analyze how relocating the planned Thirty Meter Telescope (TMT) could affect their science plans.

    TMT-Thirty Meter Telescope, proposed for Mauna Kea, Hawaii, USA

    A study looking at the consequences of such a move, which researchers will present on 31 May at a meeting of the Canadian Astronomical Society in Edmonton, finds that they’ll still be able to do most of what they want to do — but not everything.

    Legal challenges to the construction of the TMT on the Hawaiian mountain of Mauna Kea meant the international collaboration behind the facility had to consider an alternate site. But less than ideal observing conditions at their back-up site could keep scientists from pursuing what is likely to be one of the hottest topics in astronomy in the coming decade: investigating exoplanet atmospheres.

    The mega-telescope is “a critical component of the Canadian astronomical landscape,” says Michael Balogh, an astronomer at the University of Waterloo in Ontario. The country — one of six major international partners — has committed CAN$243 million (US$180 million) to the project. “If we have to move, it’s effectively a de-scope in the project,” says Balogh.
    A long, hard look

    The back-up site, Roque de los Muchachos in La Palma, the Canary Islands, is lower in elevation than Mauna Kea, and its skies are more turbulent than those above the Hawaii mountain.

    Isaac Newton Group telescopes, at Roque de los Muchachos Observatory on La Palma in the Canary Islands, Spain

    That means that observing conditions are not quite as good; in particular, the extra atmosphere above La Palma interferes with much of the observing in mid-infrared wavelengths of light, the sweet spot for looking at exoplanet atmospheres.

    See the full article here .

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    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 12:29 pm on May 31, 2017 Permalink | Reply
    Tags: , , Human embryonic stem (ES) cells, , NATURE, ,   

    From Nature: “Trials of embryonic stem cells to launch in China” 

    Nature Mag
    Nature

    31 May 2017
    David Cyranoski

    1
    Former Chinese leader Deng Xiaoping had Parkinson’s disease, one of the first targets of embryonic-stem-cell therapies being tested in China.

    In the next few months, surgeons in the Chinese city of Zhengzhou will carefully drill through the skulls of people with Parkinson’s disease and inject 4 million immature neurons derived from human embryonic stem cells into their brains. Then they will patch the patients up, send them home and wait.

    This will mark the start of the first clinical trial in China using human embryonic stem (ES) cells, and the first one worldwide aimed at treating Parkinson’s disease using ES cells from fertilized embryos. In a second trial starting around the same time, a different team in Zhengzhou will use ES cells to target vision loss caused by age-related macular degeneration.

    The experiments will also represent the first clinical trials of ES cells under regulations that China adopted in 2015, in an attempt to ensure the ethical and safe use of stem cells in the clinic. China previously had no clear regulatory framework, and many companies had used that gap as an excuse to market unproven stem-cell treatments.

    “It will be a major new direction for China,” says Pei Xuetao, a stem-cell scientist at the Beijing Institute of Transfusion Medicine who is on the central-government committee that approved the trials. Other researchers who work on Parkinson’s disease, however, worry that the trials might be misguided.

    Both studies will take place at the First Affiliated Hospital of Zhengzhou University in Henan province. In the first, surgeons will inject ES-cell-derived neuronal-precursor cells into the brains of individuals with Parkinson’s disease. The only previous trial using ES cells to treat Parkinson’s began last year in Australia; participants there received stem cells from parthenogenetic embryos — unfertilized eggs that are triggered in the lab to start embryonic development.

    In the other Zhengzhou trial, surgeons will take retinal cells derived from ES cells and transplant them into the eyes of people with age-related macular degeneration. The team will follow a similar procedure to that of previous ES-cell trials carried out by researchers in the United States and South Korea.

    Qi Zhou, a stem-cell specialist at the Chinese Academy of Sciences Institute of Zoology in Beijing, is leading both efforts. For the Parkinson’s trial, his team assessed hundreds of candidates and have so far have picked ten who best match the ES cells in the cell bank, to reduce the risk of the patients’ bodies rejecting the cells.

    The 2015 regulations state that hospitals planning to carry out stem-cell clinical work must use government-certified ES-cell lines and pass hospital-review procedures. Zhou’s team completed four years of work with a monkey model of Parkinson’s, and has met the government requirements, he says.

    Parkinson’s disease is caused by a deficit in dopamine produced by brain cells. Zhou’s team will coax ES cells to develop into precursors to neurons, and will then inject them into the striatum, a central region of the brain implicated in the disease.

    In their unpublished study of 15 monkeys, the researchers did not observe any improvements in movement at first, says Zhou. But at the end of the first year, the team examined the brains of half the monkeys and found that the stem cells had turned into dopamine-releasing cells. He says that they saw 50% improvement in the remaining monkeys over the next several years. “We have all the imaging data, behavioural data and molecular data to support efficacy,” he says. They are preparing a publication, but Zhou says that they wanted to collect a full five years’ worth of animal data.

    Maturity concerns

    Jeanne Loring, a stem-cell biologist at the Scripps Research Institute in La Jolla, California, who is also planning stem-cell trials for Parkinson’s, is concerned that the Australian and Chinese trials use neural precursors and not ES-cell-derived cells that have fully committed to becoming dopamine-producing cells. Precursor cells can turn into other kinds of neurons, and could accumulate dangerous mutations during their many divisions, says Loring. “Not knowing what the cells will become is troubling.”

    But Zhou and the Australian team defend their choices. Russell Kern, chief scientific officer of the International Stem Cell Corporation in Carlsbad, California, which is providing the cells for and managing the Australian trial, says that in preclinical work, 97% of them became dopamine-releasing cells.

    Lorenz Studer, a stem-cell biologist at the Memorial Sloan Kettering Cancer Center in New York City who has spent years characterizing such neurons ahead of his own planned clinical trials, says that “support is not very strong” for the use of precursor cells. “I am somewhat surprised and concerned, as I have not seen any peer-reviewed preclinical data on this approach,” he says.

    Studer’s and Loring’s teams are part of an international consortium that coordinates stem-cell treatments for Parkinson’s. In the next two years, five groups in the consortium plan to run trials using cells fully committed to becoming dopamine-producing cells.

    Regenerative neurobiologist Malin Parmar, who heads one of the teams at Lund University in Sweden, says that the groups “are all rapidly moving towards clinical trials, and this field will be very exciting in the coming years”.

    See the full article here .

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    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 9:02 am on May 29, 2017 Permalink | Reply
    Tags: , , , NATURE   

    From Nature: “DNA’s secret weapon against knots and tangles” 

    Nature Mag
    Nature

    19 April 2017 [Another hidden treasure comes to social media.]
    Elie Dolgin

    1
    DNA loops help to keep local regions of the genome together. M. Imakaev/G. Fudenberg/N. Naumova/J. Dekker/L. Mirny

    Leonid Mirny swivels in his office chair and grabs the power cord for his laptop. He practically bounces in his seat as he threads the cable through his fingers, creating a doughnut-sized loop. “It’s a dynamic process of motors constantly extruding loops!” says Mirny, a biophysicist here at the Massachusetts Institute of Technology in Cambridge.

    Mirny’s excitement isn’t about keeping computer accessories orderly. Rather, he’s talking about a central organizing principle of the genome — how roughly 2 metres of DNA can be squeezed into nearly every cell of the human body without getting tangled up like last year’s Christmas lights.

    He argues that DNA is constantly being slipped through ring-like motor proteins to make loops. This process, called loop extrusion, helps to keep local regions of DNA together, disentangling them from other parts of the genome and even giving shape and structure to the chromosomes.

    Scientists have bandied about similar hypotheses for decades, but Mirny’s model, and a similar one championed by Erez Lieberman Aiden, a geneticist at Baylor College of Medicine in Houston, Texas, add a new level of molecular detail at a time of explosive growth for research into the 3D structure of the genome. The models neatly explain the data flowing from high-profile projects on how different parts of the genome interact physically — which is why they’ve garnered so much attention.

    But these simple explanations are not without controversy. Although it has become increasingly clear that genome looping regulates gene expression, possibly contributing to cell development and diseases such as cancer, the predictions of the models go beyond what anyone has ever seen experimentally.

    For one thing, the identity of the molecular machine that forms the loops remains a mystery. If the leading protein candidate acted like a motor, as Mirny proposes, it would guzzle energy faster than it has ever been seen to do. “As a physicist friend of mine tells me, ‘This is kind of the Higgs boson of your field’,” says Mirny; it explains one of the deepest mysteries of genome biology, but could take years to prove.

    And although Mirny’s model is extremely similar to Lieberman Aiden’s — and the differences esoteric — sorting out which is right is more than a matter of tying up loose ends. If Mirny is correct, “it’s a complete revolution in DNA enzymology”, says Kim Nasmyth, a leading chromosome researcher at the University of Oxford, UK. What’s actually powering the loop formation, he adds, “has got to be the biggest problem in genome biology right now”.

    Loop back

    Geneticists have known for more than three decades that the genome forms loops, bringing regulatory elements into close proximity with genes that they control. But it was unclear how these loops formed.

    Several researchers have independently put forward versions of loop extrusion over the years. The first was Arthur Riggs, a geneticist at the Beckman Research Institute of City of Hope in Duarte, California, who first proposed what he called “DNA reeling” in an overlooked 1990 report[1]. Yet it’s Nasmyth who is most commonly credited with originating the concept.

    As he tells it, the idea came to him in 2000, after a day spent mountain climbing in the Italian Alps. He and his colleagues had recently discovered the ring-like shape of cohesin[2], a protein complex best known for helping to separate copies of chromosomes during cell division. As Nasmyth fiddled with his climbing gear, it dawned on him that chromosomes might be actively threaded through cohesin, or the related complex condensin, in much the same way as the ropes looped through his carabiners. “It appeared to explain everything,” he says.

    Nasmyth described the idea in a few paragraphs in a massive, 73-page review article [3]. “Nobody took notice whatsoever,” he says — not even John Marko, a biophysicist at Northwestern University in Evanston, Illinois, who more than a decade later developed a mathematical model that complemented Nasmyth’s verbal argument[4].

    Mirny joined this loop-modelling club around five years ago. He wanted to explain data sets compiled by biologist Job Dekker, a frequent collaborator at the University of Massachusetts Medical School in Worcester. Dekker had been looking at physical interactions between different spots on chromosomes using a technique called Hi-C, in which scientists sequence bits of DNA that are close to one another and produce a map of each chromosome, usually depicted as a fractal-like chessboard. The darkest squares along the main diagonal represent spots of closest interaction.

    The Hi-C snapshots that Dekker and his collaborators had taken revealed distinct compartmentalized loops, with interactions happening in discrete blocks of DNA between 200,000 and 1 million letters long[5].

    These ‘topologically associating domains’, or TADs, are a bit like the carriages on a crowded train. People can move about and bump into each other in the same carriage, but they can’t interact with passengers in adjacent carriages unless they slip between the end doors. The human genome may be 3 billion nucleotides long, but most interactions happen locally, within TADs.

    Mirny and his team had been labouring for more than a year to explain TAD formation using computer simulations. Then, as luck would have it, Mirny happened to attend a conference at which Marko spoke about his then-unpublished model of loop extrusion. (Marko coined the term, which remains in use today.) It was the missing piece of Mirny’s puzzle. The researchers gave loop extrusion a try, and it worked. The physical act of forming the loops kept the local domains well organized. The model reproduced many of the finer-scale features of the Hi-C maps.

    When Mirny and his colleagues posted their finished manuscript on the bioRxiv preprint server in August 2015, they were careful to describe the model in terms of a generic “loop-extruding factor”. But the paper didn’t shy away from speculating as to its identity: cohesin was the driving force behind the looping process for cells not in the middle of dividing, when chromosomes are loosely packed[6]. Condensin, they argued in a later paper, served this role during cell division, when the chromosomes are tightly wound[7].

    A key clue was the protein CTCF, which was known to interact with cohesin at the base of each loop of uncondensed chromosomes. For a long time, researchers had assumed that loops form on DNA when these CTCF proteins bump into one another at random and lock together. But if any two CTCF proteins could pair, why did loops form only locally, and not between distant sites?

    Mirny’s model assumes that CTCFs act as stop signs for cohesin. If cohesin stops extruding DNA only when it hits CTCFs on each side of a growing loop, it will naturally bring the proteins together.

    But singling out cohesin was “a big leap of faith”, says biophysicist Geoff Fudenberg, who did his PhD in Mirny’s lab and is now at the University of California, San Francisco. “No one has seen these motors doing these things in living cells or even in vitro,” he says. “But we see all of these different features of the data that line up and can be unified under this principle.”

    Experiments had shown, for example, that reducing the amount of cohesin in a cell results in the formation of fewer loops[8]. Overactive cohesin creates so many loops that chromosomes smush up into structures that resemble tiny worms[9].

    The authors of these studies had trouble making sense of their results. Then came Mirny’s paper on bioRxiv. It was “the first time that a preprint has really changed the way people were thinking about stuff in this field”, says Matthias Merkenschlager, a cell biologist at the MRC London Institute of Medical Sciences. (Mirny’s team eventually published the work in May 2016, in Cell Reports [6].)

    Multiple discovery?

    Lieberman Aiden says that the idea of loop extrusion first dawned on him during a conference call in March 2015. He and his former mentor, geneticist Eric Lander of the Broad Institute in Cambridge, Massachusetts, had published some of the most detailed, high-resolution Hi-C maps of the human genome available at the time[10].

    During his conference call, Lieberman Aiden was trying to explain a curious phenomenon in his data. Almost all the CTCF landing sites that anchored loops had the same orientation. What he realized was that CTCF, as a stop sign for extrusion, had inherent directionality. And just as motorists race through intersections with stop signs facing away from them, so a loop-extruding factor goes through CTCF sites unless the stop sign is facing the right way.

    His lab tested the model by systematically deleting and flipping CTCF-binding sites, and remapping the chromosomes with Hi-C. Time and again, the data fitted the model. The team sent its paper for review in July 2015 and published the findings three months later [11].

    Mirny’s August 2015 bioRxiv paper didn’t have the same level of experimental validation, but it did include computer simulations to explain the directional bias of CTCF. In fact, both models make essentially the same predictions, leading some onlookers to speculate on whether Mirny seeded the idea. Lieberman Aiden insists that he came up with his model independently. “We submitted our paper before I ever saw their manuscript,” he says.

    There are some tiny differences. The cartoons Mirny uses to describe his model seem to suggest that one cohesin ring does the extruding, whereas Lieberman Aiden’s contains two rings, connected like a pair of handcuffs (see ‘The taming of the tangles’). Suzana Hadjur, a cell biologist at University College London, calls this mechanistic nuance “absolutely fundamental” to determining cohesin’s role in the extrusion process.

    2
    Nik Spencer/Nature

    Neither Lieberman Aiden nor Mirny say they have a strong opinion on whether the system uses one ring or two, but they do differ on cohesin’s central contribution to loop formation. Mirny maintains that the protein is the power source for looping, whereas Lieberman Aiden summarily dismisses this idea. Cohesin “is a big doughnut”, he says. It doesn’t do that much. “It can open and close, but we are very, very confident that cohesin itself is not a motor.”

    Instead, he suspects that some other factor is pushing cohesin around, and many in the field agree. Claire Wyman, a molecular biophysicist at Erasmus University Medical Centre in Rotterdam, the Netherlands, points out that cohesin is only known to consume small amounts of energy for clasping and releasing DNA, so it’s a stretch to think of it motoring along the chromosome at the speeds required for Mirny’s model to work. “I’m willing to concede that it’s possible,” she says. “But the Magic 8-Ball would say that, ‘All signs point to no’.”

    One group of proteins that might be doing the pushing is the RNA polymerases, the enzymes that create RNA from a DNA template. In a study online in Nature this week[12], Jan-Michael Peters, a chromosome biologist at the Research Institute of Molecular Pathology in Vienna, and his colleagues show that RNA polymerases can move cohesin over long distances on the genome as they transcribe genes into RNA. “RNA polymerases are one type of motor that could contribute to loop extrusion,” Peters says. But, he adds, the data indicate that it cannot be the only force at play.

    Frank Uhlmann, a biochemist at the Francis Crick Institute in London, offers an alternative that doesn’t require a motor protein at all. In his view, a cohesin complex might slide along DNA randomly until it hits a CTCF site and creates a loop. This model requires only nearby strands of DNA to interact randomly — which is much more probable, Uhlmann says. “We do not need to make any assumptions about activities that we don’t have experimental evidence for.”

    Researchers are trying to gather experimental evidence for one model or another. At the Lawrence Livermore National Laboratory in California, for example, biophysicist Aleksandr Noy is attempting to watch loop extrusion in action in a test tube. He throws in just three ingredients: DNA, some ATP to provide energy, and the bacterial equivalent of cohesin and condensin, a protein complex known as SMC.

    “We see evidence of DNA being compacted into these kinds of flowers with loops,” says Noy, who is collaborating with Mirny on the project. That suggests that SMC — and by extension cohesin — might have a motor function. But then again, it might not. “The truth is that we just don’t know at this point,” Noy says.

    Bacterial battery

    The experiment that perhaps comes the closest to showing cohesin acting as a motor was published in February[13]. David Rudner, a bacterial cell biologist at Harvard Medical School in Boston, Massachusetts, and his colleagues made time-lapse Hi-C maps of the bacterium Bacillus subtilis that reveal SMC zipping along the chromosome and creating a loop at a rate of more than 50,000 DNA letters per minute. This tempo is on par with what researchers estimate would be necessary for Mirny’s model to work in human cells as well.

    Rudner hasn’t yet proved that SMC uses ATP to make that happen. But, he says, he’s close — and he would be “shocked” if cohesin worked differently in human cells.

    For now, the debate rages about what cohesin is, or is not, doing inside the cell — and many researchers, including Doug Koshland, a cell biologist at the University of California, Berkeley, insist that a healthy dose of scepticism is still warranted when it comes to Mirny’s idea. “I am worried that the simplicity and elegance of the loop-extrusion model is already filling textbooks, coronated long before its time,” he says.

    And although it may seem an academic dispute among specialists, Mirny notes that if it his model is correct, it will have real-world implications. In cancer, for instance, cohesin is frequently mutated and CTCF sites altered. Defective versions of cohesin have also been implicated in several rare human developmental disorders. If the loop-extruding process is to blame, says Mirny, then perhaps a better understanding of the motor could help fix the problem.

    But his main interest remains more fundamental. He just wants to understand why DNA is configured in the way it is. And although his model assumes a lot of things about cohesin, Mirny says, “The problem is that I don’t know any other way to explain the formation of these loops.”

    References
    See the full article for 13 references with links.

    See the full article here .

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

    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 .

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  • richardmitnick 10:24 pm on May 20, 2017 Permalink | Reply
    Tags: , G-d and Organized Religion, G-d and Science, , NATURE, Pope Francis   

    From Nature: “Keep doors open for constructive dialogue between religion and science” 

    Nature Mag
    Nature

    15 May 2017
    Editorial – No writer credit. How does that work?

    [There is no chasm between Science and G-d, only between Science and Organized Religion. One day, Science will find G-d. It took 60 years and €12 billion to find the Higgs Boson. That is nothing compared to the ultimate search for G-d, who created everything.]

    A meeting between the Pope, patients and researchers acknowledges how the two sectors can help each other.

    1
    People in developing nations are aiding research into the genetics behind Huntington’s disease. Dara Mohammadi

    Dilia is the oldest of an unusual crowd of people due to meet Pope Francis this week at the Vatican. The 79-year-old widow from rural Colombia married into a family whose members carry the gene for Huntington’s disease, a hereditary neurodegenerative disorder. Fate was cruel. Of her 11 children, 9 inherited the disease. Five have died and the remaining four are sick. The next generation is affected, too. One grandchild has died and five more show symptoms.

    Those symptoms — involuntary, jerky movements accompanied by mood swings and cognitive decline — are aggressive and carry stigma. Patients and their families often live out of sight and in dreadful conditions, especially in developing nations. Dilia’s village has limited access to running water.

    Despite their own hardship, many have helped research into the condition — with little tangible reward. Most of them are Catholics, so their meeting with Pope Francis is a thank you from the scientists who arranged the event. These researchers are acutely aware of how much they have relied on the patients — the gene that causes Huntington’s was discovered thanks to tissue donations from poor Venezuelan families — and that they have not been able to do anything to change their dire situation.

    The fact that Pope Francis quickly agreed to meet the families speaks to his hallmark philosophy of reaching out to poor and disadvantaged people. But it is also further evidence of a new openness towards science, which has followed a 2015 encyclical — a letter of guidance on particular themes written by a pope to his bishops — called Laudato si’. The encyclical argued for better stewardship of the planet and excited scientists with its forthright pronouncements on the need to control greenhouse gases and with its implicit acceptance of the principles of evolution in well-informed discussion of the need to protect biodiversity. It also acknowledges the value of scientific and academic freedom in society, and the need for open scientific debate on advances in biology.

    The Huntington’s event is a gesture that shows in a small but significant way in which religious leaders and science can work towards a common goal.

    While the Vatican has supported its elite Pontifical Academy of Sciences for more than 80 years, other grass-roots initiatives are emerging.

    1

    For example, last month Italian researchers collaborated with The Lancet to organize a conference in Rome called (with undeniable hubris) The Future of Humanity Through the Lens of Medical Science. Attended by Nobel laureates and Vatican officials, its discussions ranged beyond biomedicine to encompass themes such as climate change and migration, mirroring the spectrum of Laudato si’.

    There is a chasm between religion and science that cannot be bridged. For all its apparent science-friendliness, Laudato si’ sticks to the traditional Vatican philosophy that the scientific method cannot deliver the full truth about the world. However, there is still much to be discussed on how each side can help the other to converge on shared goals.

    The Catholic Church has more than 1.2 billion members and can thus have broad influence on the acceptance of facts that some politicians choose to distort — such as the existence of anthropogenic climate change. Scientists can provide technical solutions for poor and sick people, thereby assisting the work of missionaries.

    In Rome, Huntington’s researchers still desperately seeking a treatment for the disease will have an opportunity to discuss with Pope Francis sensitive issues relating to avoidance of the disease, namely contraception and embryo selection. Francis rarely misses an opportunity to reiterate his view of the sanctity of the human embryo (a theologically debatable Vatican position that has hindered important stem-cell research in some countries) but he seems to keep his views on contraception — outlawed by the Church — deliberately ambiguous. The special audience may help to encourage a much-needed move from the Vatican towards the mercy (and reality — Catholics in rich countries routinely ignore the ban) of finally allowing followers, including those with devastating hereditary disease, to take control of their fertility.

    See the full article here .

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

    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 .

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