From Medscape via Broad: Women in Stem- “Outbreaks, Evolution, and Rock ‘n’ Roll: Topol Talks to Pardis Sabeti”

Broad Institute

Broad Institute

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Medscape

May 10, 2017
Eric J. Topol, MD

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Pardis Sabeti

Eric J. Topol, MD: Hello. I am Eric Topol, editor-in-chief of Medscape. I have the special privilege of having a conversation with Pardis Sabeti. She is an extraordinary scientist and physician at the Broad Institute at Harvard Medical School and MIT. We are going to talk about the arc of her life and career, beginning when she moved here at age 2 from Tehran.

Pardis Sabeti, MD, DPhil: Yes. We came to the United States around the time of the Iranian revolution and had refugee status here. Then we moved to Hawaii, New Jersey, Georgia, and Florida, and we settled in Florida.

Dr Topol: At one point you were not sure whether you were going to own a flower shop, be a novelist, or become a doctor. Is that right?

Dr Sabeti: That was when I was about 6 years old. I liked flowers a lot, so I thought, “This seems like the life.” As a kid, I liked to write. As an immigrant and as a child of revolution, my dad amused himself by saying, “You can be anything you want to be in the world: a lawyer or a doctor.” My sister became a lawyer and I became a doctor, but neither of us practice.

Dr Topol: Music has been a big part of your life. When did that become rooted?

Dr Sabeti: That was not until graduate school. I have liked music my whole life and played a little piano as a kid. I went to concerts all the time. That was how I enjoyed spending my time. When I was in grad school, I had two American friends and we were in England together. They would play “fantasy band” all the time and make up band names and that kind of stuff. One night I said, “Why do you keep fantasy-banding? Why not just start a band?” They said they at least had to have a rhythm section, so the next day I bought a bass and that started my journey.

Dr Topol: These days, you are a lead singer and writer for a rock band. How often do you get involved with that?

Dr Sabeti: It wanes and waxes. It’s not very conducive to faculty life. I dropped it for a while and then I had an accident and picked it up again. Music is great, because every once in a while your soul just wants to speak and you have an opportunity to do it. It’s pretty sporadic, but I have been writing some music recently.

Dr Topol: Somehow or other, you landed at MIT.

Dr Sabeti: In the 6th grade, the idea of going to MIT got sparked. My math teacher showed us a 270 competition: The MIT mechanical engineering department has a contest in which everyone builds robots that compete against each other. I saw that video as a kid and thought, “I need to be there.” I was locked onto MIT as my dream school since then.

Dr Topol: You also became a Rhodes Scholar and went to Oxford.

Dr Sabeti: It was a bizarre experience right after college to be in this wonderland that was Oxford, and a lot of existential crises happened right after college. It was a very informative and great experience.

Dr Topol: Were you already starting to get into the whole selection, mutation, and evolutionary biology by then?

Dr Sabeti: No. I think that is what made that happen. I had gone to MIT and I loved all the engineering, but I still thought that I was supposed to be a doctor. I had intended to go to medical school, but I got this scholarship on a lark. I was planning to go to medical school when I came back. Along the way, somehow, I ended up getting a PhD. It was an interesting experience there. They had a shorter PhD track. That was when I started doing that work, and it changed the direction of my life.

In the Middle of an Outbreak

Dr Topol: And then you went to medical school—a big commitment. When you started your career, did you know that you were going to be leading the charge to do genomic epidemiology of Ebola and Zika?

Dr Sabeti: Definitely not. Because I never intended to be a scientist, I didn’t have a very specific path for what I wanted to do. I feel like I am on a scavenger hunt; I don’t know exactly where it’s going, but this path has captured my attention for some time.

Dr Topol: This is quite a hunt. Just what you did with Ebola—you were named a Time “Person of the Year” in 2014 and one of the 100 most influential people in the world. You went to West Africa with folks in your lab, and many other people you work with, to try to get the knowledge that was needed to titrate the horrendous Ebola epidemic. Can you tell us about that?

Dr Sabeti: Sure. For one thing, I am just a bit player. At the end of the day, the Ebola fighters were recognized for the work that we all did collectively. I was privileged to be one of the people who were named as an example, but it was a collective effort. To us, the seemingly small part that we played was that we naturally come from the genomics world—I cut my teeth on the Human Genome Project—where sharing data and an open feeling about science was just a given.

This is an outbreak that we found ourselves in the middle of because it came to the site where we were working in Africa. As we were trying to do what we could to help our collaborators and partners there, and to get attention, we started publishing science on this. We started releasing our data to the lab. What was interesting is that we decided we didn’t care about getting recognition; we just wanted to get the data out to the world. Paradoxically, that is what got us attention. It was apparently unusual to share data openly as soon as you generated it. It became a call to the community.

Dr Topol: You were putting your lives on the line to do this work. What was that like?

Dr Sabeti: To be honest, as a scientist, that is the risk you take. We were working on Lassa fever for some time. I have been quarantined before. We take risks, but they are very measured, calculated risks. Fundamentally, in all cases, it was the clinicians who became infected. We saw that across the board in the outbreak. As the researchers, we work in a very contained environment and we can isolate things very well. We are really in the service of the clinicians. We take risks, but for us, there was more risk of being in a car crash than being infected with Ebola. We were honored to be there to support them.

Dr Topol: More recently, you have been involved with the Zika virus story. Where do we stand with that?

Dr Sabeti: Zika is different. Ebola was a rapidly escalating outbreak. It was one of those viruses that can transmit from human to human with very acute infections and a very high fatality rate. It was a frightening event. Zika is less fatal. It does not transmit as easily. It usually involves mosquitoes. But it is a more challenging virus to battle; it’s more widespread, and mosquitoes are hard to manage. The virus hides itself a little at low concentrations in the blood for short periods of time, so the diagnosis is challenging. But it becomes really important because of the effects it can have on pregnancy and on children born to mothers who have Zika. Zika causes a visceral reaction in all of us because it affects a vulnerable population that we all care about.

Please Play With Our Data

Dr Topol: In 2015 you gave a TED Talk on how we are going to deal with the next deadly virus. Can you summarize what you talked about at the time?

Dr Sabeti: That was in the middle of the Ebola outbreak. I had been asked to give a talk at TEDWomen. I just discussed what was on my mind at the time. I had not really thought out exactly what the message would be, and I did not know, necessarily, that it would be posted online. In fact, I sang during my talk. It was good in the room, but they wanted to cut it out and make it the right length [for TED Talks online]. I just had fun with it. The message was about outbreaks and how frightening they are. But it’s a war that we can win—but that we win by collaboration. It is very different from other types of threats to humanity. That was what I felt—the power of human capacity and love to overcome these kinds of challenges.

See the full article here .

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Visit World Community Grid (WCG). Download and install the BOINC software on which it runs. Attach to the Outsmart Ebola Together project. This will allow WCG to use your computer’s free CPU cycles to process computational data for the project.

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YOU CAN HELP FIND A CURE FOR THE ZIKA VIRUS.

There is a new project at World Community Grid [WCG] called OpenZika.
Zika
Zika depiction. Image copyright John Liebler, www.ArtoftheCell.com
Rutgers Open Zika

WCG runs on your home computer or tablet on software from Berkeley Open Infrastructure for Network Computing [BOINC]. Many other scientific projects run on BOINC software.Visit WCG or BOINC, download and install the software, then at WCG attach to the OpenZika project. You will be joining tens of thousands of other “crunchers” processing computational data and saving the scientists literally thousands of hours of work at no real cost to you.

This project is directed by Dr. Alexander Perryman a senior researcher in the Freundlich lab, with extensive training in developing and applying computational methods in drug discovery and in the biochemical mechanisms of multi-drug-resistance in infectious diseases.

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Dr. Alex Perryman, Rutgers New Jersey Medical School

He is a member of the Center for Emerging & Re-emerging Pathogens, in the Department of Pharmacology, Physiology, and Neuroscience, at the Rutgers University, New Jersey Medical School. Previously, he was a Research Associate in Prof. Arthur J. Olson’s lab at The Scripps Research Institute (TSRI), where he ran the day-to-day operations of the FightAIDS@Home project, the largest computational drug discovery project devoted to HIV/AIDS, which also runs on WCG. While in the Olson lab, he also designed, led, and ran the largest computational drug discovery project ever performed against malaria, the GO Fight Against Malaria project, also on WCG.

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From OpenZika at WCG: “OpenZika Researchers Continue Calculations and Prepare for Next Stage”

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World Community Grid (WCG)

By: The OpenZika research team
21 Mar 2017

Summary
The OpenZika researchers are continuing to screen millions of chemical compounds as they look for potential treatments for the Zika virus. In this update, they report on the status of their calculations and their continuing work to spread the word about the project.

Zika depiction. Image copyright John Liebler, www.ArtoftheCell.com

Project Background

While the Zika virus may not be getting the continuous press coverage that it received in 2015 and 2016, it is still a threat to the health of people across the globe. New infections continue to be reported in both South America and North America, and medical workers are just beginning to assess the effects of the virus on young children whose mothers were infected while pregnant.

The search for effective treatments is crucial to stemming the tide of the virus. In addition to the OpenZika project, several other labs are doing cell-based screens with drugs already approved by the US Food and Drug Administration (FDA) agency, but few to none of the “hit” compounds that have been identified thus far are both potent enough against Zika virus and also safe for pregnant women.

Also, there are a number of efforts underway to develop a vaccine against the Zika virus. However, vaccines do not help people who already have the infection. It will be several years before they are proven effective and safe, and before enough doses can be mass produced and distributed. And even after approved vaccines are available and distributed to the public, not all people will be vaccinated. Consequently, in the meantime and in the future, cures for Zika infections are needed.

ZIKV NS3 helicase bound to RNA with the predicted binding modes of five approved drugs (from our second set of candidates) selected by virtual screening. These candidates are shown as surfaces with different shades of green. The identification of these candidates and the video were made by Dr. Alexander L. Perryman [see below].

We began the analysis phase of the project by focusing on the results against the apo NS3 helicase crystal structure (apo means that the protein was not bound to anything else, such as a cofactor, inhibitor, or nucleic acid) to select our first set of candidates, which are currently being assayed by our collaborator at University of California San Diego, Dr. Jair L. Siqueira-Neto, using cell-based assays. The NS3 helicase is a component of the Zika virus that is required for it to replicate itself.

In the second set of screening results that we recently examined, we used the new crystal structure of NS3 helicase bound to RNA as the target (see the images / animation above). Similar to the first set of candidates, we docked approximately 7,600 compounds in a composite library composed of the US Food and Drug Administration-approved drugs, the drugs approved in the European Union, and the US National Institutes of Health clinical collection library against the new RNA-bound structure of the helicase. Below are the results of this second screening:

232 compounds passed the larger collection of different energetic and interaction-based docking filters, and their predicted binding modes were inspected and measured in detail.
Of the compounds that were inspected in detail, 19 unique compounds passed this visual inspection stage of their docked modes.
From the compounds that passed the visual inspection, 9 passed subsequent medicinal chemistry-based inspection and will be ordered soon.

Status of the calculations

In total, we have submitted 2.56 billion docking jobs, which involved the virtual screening of 6 million compounds versus 427 different target sites. We have already received approximately 1.9 billion of these results on our server. (There is some lag time between when the calculations are performed on your volunteered machines and when we get the results, since all of the results per “package” of approximately 10,000 different docking jobs need to be returned to World Community Grid, re-organized, and then compressed before sending them to our server.)

Except for a few stragglers, we have received all of the results for our experiments that involve docking 6 million compounds versus the proteins NS1, NS3 helicase (both the RNA binding site and the ATP site), and NS5 (both the RNA polymerase and the methyltransferase domains). We are currently receiving the results from our most recent experiments against the NS2B / NS3 protease.

A new stage of the project

We just finished preparing and testing the docking input files that will be used for the second stage of this project. Instead of docking 6 million compounds, we will soon be able to start screening 30.2 million compounds against these targets. This new, massive library was originally obtained in a different type of format from the ZINC15 server. It represents almost all of “commercially available chemical space” (that is, almost all of the “small molecule” drug-like and hit-like compounds that can be purchased from reputable chemical vendors).

The ZINC15 server provided these files as “multi-molecule mol2” files (that is, many different compounds were contained in each “mol2” formatted file). These files had to be re-formatted (we used the Raccoon program from Dr. Stefano Forli, who is part of the FightAIDS@Home team) by splitting them into individual mol2 files (1 compound per file) and then converting them into the “pdbqt” docking input format.

We then ran a quick quality control test to make sure that the software used for the project, called AutoDock Vina, could properly use each pdbqt file as an input. Many compounds had to be rejected, because they had types of atoms that cause Vina to crash (such as silicon or boron), and we obviously don’t want to waste the computer time that you donate by submitting calculations that will crash.

By splitting, reformatting, and testing hundreds of thousands of compounds per day, day after day, after approximately six months this massive new library of compounds is ready to be used in our OpenZika calculations. Without the tremendous resources that World Community Grid volunteers provide for this project, we would not even dream of trying to dock over 30 million compounds against many different targets from the Zika virus. Thank you all very much!!!

For more information about these experiments, please visit our website.

Our PLoS Neglected Tropical Diseases paper, OpenZika: An IBM World Community Grid Project to Accelerate Zika Virus Drug Discovery, was published on October 20, and it has already been viewed over 4,000 times. Anyone can access and read this paper for free. Another research paper Illustrating and homology modeling the proteins of the Zika virus has been accepted by F1000Research and viewed > 3800 times.

A group from Brazil, coordinated by Prof. Glaucius Oliva, has contacted us because of our PLoS Neglected Tropical Diseases paper to discuss a new collaboration to test the selected candidate compounds directly on enzymatic assays with the NS5 protein of Zika virus. They have solved two high-resolution crystal structures of ZIKV NS5, which have been recently released on the PDB (Protein Data Bank) (PDB ID: 5TIT and 5U04).

Our paper entitled “Molecular Dynamics simulations of Zika Virus NS3 helicase: Insights into RNA binding site activity” was just accepted for publication in a special issue on Flaviviruses for the journal Biochemical and Biophysical Research Communications. This study of the NS3 helicase system helped us learn more about this promising target for blocking Zika replication. The results will help guide how we analyze the virtual screens that we already performed against NS3 helicase, and the molecular dynamics simulations generated new conformations of this protein that we will use as input targets in new virtual screens that we perform as part of OpenZika.

Additional News

We have applied and been accepted to present OpenZika: Opening the Discovery of New Antiviral candidates against Zika Virus and Insights into Dynamic behavior of NS3 Helicase to the 46th World Chemistry Congress. The conference will be held in Sao Paulo, Brazil, on July 7-14.

Dr. Sean Ekins has hired a postdoc and a master level scientist who will get involved with the OpenZika project. We have also started to collate literature inhibitors from Zika papers.

Also, Drs. Sean Ekins and Carolina Andrade have offered to buy some of the candidate compounds that we identified in the virtual screens from OpenZika, so that they can be assayed in the next round of tests.


Dr. Alex Perryman models an OpenZika shirt. Profits from the sale of OpenZika merchandise go to purchasing compounds for lab testing. (Photo by Keith Bratcher, courtesy of Rutgers University)

Alexander L. Perryman, Ph.D., is a senior researcher (Research Teaching Specialist III) in the lab, with extensive training in computational methods in drug discovery and in the biochemical mechanisms of multi-drug-resistance in infectious diseases. He is a member of the Center for Emerging & Re-emerging Pathogens, in the Department of Pharmacology, Physiology & Neuroscience. Alex started performing research in Professor Cleo Samudzi’s X-ray crystallography lab as a freshman in the undergraduate Biochemistry program at the University of Missouri-Columbia (“Mizzou” or MU). He then became a Beckman Scholar in Professor Thomas P. Quinn’s protein structure & radiopharmaceuticals lab at MU. He received his Ph.D. in Biomedical Sciences from the University of California, San Diego (UCSD) School of Medicine (Pharmacology Department) as a Howards Hughes Medical Institute fellow in H.H.M.I. Principal Investigator J. Andrew McCammon’s lab. As a graduate student, Alex used Molecular Dynamics simulations to (a) predict a mechanism of multi-drug-resistance for “super bug” mutants of HIV protease, (b) to predict the existence of allosteric binding sites on the surface of HIV protease and then (c) to test the utility of exploiting that allosteric relationship. These predictions are now supported by an ever-growing body of experimental evidence. He also helped create the “Relaxed Complex Scheme,” which was one of the first methods to incorporate the flexibility of the target protein into docking studies of potential drug-like compounds. He conducted post-doctoral research at the California Institute of Technology (“Caltech”) as an Amgen fellow in the Division of Biology. He then became a Research Associate in Prof. Arthur J. Olson’s lab at The Scripps Research Institute (TSRI), where he ran the day-to-day operations of the FightAIDS@Home project (the largest computational drug discovery project devoted to HIV/AIDS, which runs on IBM’s World Community Grid). He also designed, led, and ran the day-to-day operations for the largest computational drug discovery project ever performed against malaria, the GO Fight Against Malaria project, also on IBM’s World Community Grid. GO FAM involved screening 5.6 million compounds against 22 different classes of drug targets (including targets from Mycobacterium tuberculosis, as well). GO Fight Against Malaria was the first academic project to ever perform over 1 billion different docking jobs. His experience is highlighted by over 24 publications and one US patent.

In the Freundlich lab, Alex has broadened his experience by becoming an expert at developing and applying machine learning models and other ligand-based techniques to advance Mtb research, as well as projects against the ESKAPE pathogens. He has also created several machine learning models to help address key shortcomings in chemical tool discovery and drug development (such as metabolic stability, cytotoxicity, and solubility). For a change, Dr. Perryman has also been getting his hands wet–purifying proteins and performing enzyme inhibition assays, to help test his new computational predictions against Mtb targets.

See the full article here.

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From UCLA: “Zika-linked birth defects more extensive than previously thought, UCLA-led research finds”

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UCLA

December 15, 2016
Enrique Rivero

New UCLA-led research finds that Zika-linked abnormalities that occur in human fetuses are more extensive — and severe — than previously thought, with 46 percent of 125 pregnancies among Zika-infected women resulting in birth defects in newborns or ending in fetal death.

The study, published in the New England Journal of Medicine, suggests that damage during fetal development from the mosquito-borne virus can occur throughout pregnancy and that other birth defects are more common than microcephaly, when babies are born with very small heads. Further, these defects may only be detected weeks or months after the baby is born, said Dr. Karin Nielsen, the study’s senior author and a professor of clinical pediatrics in the division of pediatric infectious diseases at the David Geffen School of Medicine at UCLA and Mattel Children’s Hospital.

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Dr. Karin Nielsen. UCLA

“This means that microcephaly is not the most common congenital defect from the Zika virus,” Nielsen said. The absence of that condition does not mean the baby will be free of birth defects, she added, because “there are problems that are not apparent at birth” and such difficulties may not be evident until the age of six months.

“These are sobering results,” Nielsen said.

The results are a follow-up to a smaller Brazilian study published in March that used molecular testing to find an association between Zika infection in pregnant women and a series of serious outcomes that included fetal deaths (miscarriages and stillbirths), abnormal fetal growth and damage to the central nervous system. This is the largest study to date of Zika-affected pregnancies in which the women were followed from the time they were infected to the end of their pregnancies. All the women were enrolled before any abnormalities in their pregnancies had been identified.

The new study was based on a larger sample size of 345 women in Rio de Janeiro, Brazil, who were enrolled from September 2015 through May 2016. Of those women, 182, or 53 percent, tested positive for Zika in the blood, urine or both. In addition, 42 percent of the women who did not have Zika were found to be infected with chikungunya, another mosquito-borne virus; 3 percent of Zika-positive women also had chikungunya.

From there, the researchers evaluated 125 women infected with Zika and 61 who were not infected with the virus who had given birth by July 2016. The previous study was based mainly on prenatal ultrasound findings; by contrast, the current research evaluated infants from Zika-affected pregnancies through physical examination and brain imaging. Among the findings:

There were nine fetal deaths among women with Zika infection during pregnancy, five of those in the first trimester.
Fetal deaths or abnormalities in the infants were present in 46 percent of Zika-positive women, contrasted with 11.5 percent of Zika-negative women.
Forty-two percent of infants born to the Zika-infected mothers were found to have microcephaly, brain lesions or brain calcifications seen in imaging studies, lesions in the retina, deafness, feeding difficulties and other complications.

The risks occurred at all stages of pregnancy: 55 percent of pregnancies were affected in the first trimester, 51 percent in the second trimester and 29 percent in the third trimester.

The researchers noted that they examined the babies during their early infancy, when “more subtle neurologic manifestations of disease are not identified.” So follow-up examinations could turn up evidence of more neurologic diseases that couldn’t be detected earlier in the babies’ lives.

“Our data show that the risk of severe adverse pregnancy and infant outcomes after maternal Zika infection was substantial,” the authors wrote.

Supporting the study were the Departamento de Ciência e Tecnologia do Ministério da Saúde do Brasil; Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES/ 88887.116627/2016-01,) and the National Institute of Allergy and Infectious Diseases/National Institutes of Health grant AI AI28697.

See the full article here .

YOU CAN HELP FIND A CURE FOR THE ZIKA VIRUS.

There is a new project at World Community Grid [WCG] called OpenZika.
Zika
Zika depiction. Image copyright John Liebler, www.ArtoftheCell.com
Rutgers Open Zika

WCG runs on your home computer or tablet on software from Berkeley Open Infrastructure for Network Computing [BOINC]. Many other scientific projects run on BOINC software.Visit WCG or BOINC, download and install the software, then at WCG attach to the OpenZika project. You will be joining tens of thousands of other “crunchers” processing computational data and saving the scientists literally thousands of hours of work at no real cost to you.

This project is directed by Dr. Alexander Perryman a senior researcher in the Freundlich lab, with extensive training in developing and applying computational methods in drug discovery and in the biochemical mechanisms of multi-drug-resistance in infectious diseases. He is a member of the Center for Emerging & Re-emerging Pathogens, in the Department of Pharmacology, Physiology, and Neuroscience, at the Rutgers University, New Jersey Medical School. Previously, he was a Research Associate in Prof. Arthur J. Olson’s lab at The Scripps Research Institute (TSRI), where he ran the day-to-day operations of the FightAIDS@Home project, the largest computational drug discovery project devoted to HIV/AIDS, which also runs on WCG. While in the Olson lab, he also designed, led, and ran the largest computational drug discovery project ever performed against malaria, the GO Fight Against Malaria project, also on WCG.

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This can-do perspective has brought us 12 Nobel Prizes, 12 Rhodes Scholarships, more NCAA titles than any university and more Olympic medals than most nations. Our faculty and alumni helped create the Internet and pioneered reverse osmosis. And more than 100 companies have been created based on technology developed at UCLA.

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From NYT: “Colombia Reports Major Rise in Birth Defect Amid Zika Crisis”

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The New York Times

DEC. 10, 2016
DONALD G. McNEIL Jr.

Colombia, which suffered a Zika epidemic that peaked in February, has reported four times as many cases of babies born with microcephaly this year as it did in 2015, providing more proof that the Zika virus causes brain damage in infants.

Because births of microcephalic infants peaked five months after the epidemic did, at about nine times the numbers of the previous July, scientists feel sure that the greatest risk is to babies whose mothers were infected during their first trimesters or early in their second.

The numbers were reported in a study released Friday by the Centers for Disease Control and Prevention and conducted jointly by scientists from the C.D.C. and Colombia’s national health institute.

With 105,000 suspected Zika cases, Colombia has had the second-largest Zika epidemic after Brazil. Brazil has had proportionally many more cases of microcephaly, and the reason has remained a mystery, although its population is four times larger than Colombia’s and it experienced a much longer, more intense epidemic in 2014 and 2015, especially in the northeast.

As of Thursday, Brazil had reported 2,211 cases of microcephaly in which Zika infection had been confirmed to the World Health Organization, while Colombia had reported only 60.

W.H.O. reports of confirmed cases have sometimes lagged weeks behind local reports. The study released by the C.D.C. found 476 cases of microcephaly in Colombia between January and mid-November. Of those, only 147 — about 30 percent — had laboratory evidence of Zika virus infection. But many others were not tested, and the virus is not always detectable months after it damages a fetus, so the true numbers may be higher.

About 4 percent of the fetuses tested had evidence of other infections that can cause microcephaly, such as toxoplasmosis, herpes, cytomegalovirus or syphilis. Many other fetuses were not tested or their microcephaly had no clear cause.

Of the total, 432 of the microcephaly cases were in babies born alive, and 44 were in fetuses that were stillborn, miscarried or aborted. One theory — still unproven — is that Colombia had fewer microcephaly cases than expected because many fearful women aborted their pregnancies, legally or illegally. Abortion is much more restricted in Brazil than in Colombia.

The number of confirmed cases of microcephaly is in line with predictions made by health officials after they declared an end to the Zika epidemic in Colombia in July. Early in the year, based on Brazil’s experience, Dr. Fernando Ruiz, the vice minister for public health, estimated that Colombia would have 700 cases of Zika-related microcephaly this year. In August, he changed that estimate to between 100 and 250.

Although Colombia is widely believed to have a better disease-surveillance system than Brazil, it still relies on doctors to voluntarily report birth defects. They may have been underreported in 2015, before microcephaly was in the news.

See the full article here .

YOU CAN HELP FIND A CURE FOR THE ZIKA VIRUS.

There is a new project at World Community Grid [WCG] called OpenZika.
Zika
Zika depiction. Image copyright John Liebler, www.ArtoftheCell.com
Rutgers Open Zika

WCG runs on your home computer or tablet on software from Berkeley Open Infrastructure for Network Computing [BOINC]. Many other scientific projects run on BOINC software.Visit WCG or BOINC, download and install the software, then at WCG attach to the OpenZika project. You will be joining tens of thousands of other “crunchers” processing computational data and saving the scientists literally thousands of hours of work at no real cost to you.

This project is directed by Dr. Alexander Perryman a senior researcher in the Freundlich lab, with extensive training in developing and applying computational methods in drug discovery and in the biochemical mechanisms of multi-drug-resistance in infectious diseases. He is a member of the Center for Emerging & Re-emerging Pathogens, in the Department of Pharmacology, Physiology, and Neuroscience, at the Rutgers University, New Jersey Medical School. Previously, he was a Research Associate in Prof. Arthur J. Olson’s lab at The Scripps Research Institute (TSRI), where he ran the day-to-day operations of the FightAIDS@Home project, the largest computational drug discovery project devoted to HIV/AIDS, which also runs on WCG. While in the Olson lab, he also designed, led, and ran the largest computational drug discovery project ever performed against malaria, the GO Fight Against Malaria project, also on WCG.

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#colombia-reports-major-rise-in-birth-defect-amid-zika-crisis, #nyt, #openzika-project-at-world-community-grid, #zika

From Harvard Medical School: “Zika’s Entry Points”

Harvard University
Harvard University

harvard-medical-school-bloc

Harvard Medical School

December 1, 2016
HANNAH ROBBINS
ERIC BENDER

Fast-spreading virus can take multiple routes into the growing brain.

1
Zika virus (light blue) spreads through a three-dimensional model of a developing brain. Image: Max Salick and Nathaniel Kirkpatrick/Novartis

Around the world, hundreds of women infected with the Zika virus have given birth to children suffering from microcephaly or other brain defects, as the virus attacks key cells responsible for generating neurons and building the brain as the embryo develops.

Studies have suggested that Zika enters these cells, called neural progenitor cells or NPCs, by grabbing onto a specific protein called AXL on the cell surface. Now scientists at the Harvard Stem Cell Institute (HSCI) and Novartis have shown that this is not the only route of infection for NPCs.

The scientists demonstrated that the Zika virus infected NPCs even when the cells did not produce the AXL surface receptor protein that is widely thought to be the main vehicle of entry for the virus.

“Our finding really recalibrates this field of research, because it tells us we still have to go and find out how Zika is getting into these cells,” said Kevin Eggan, principal faculty member at HSCI, professor of stem cell and regenerative biology at Harvard University’s Faculty of Arts and Sciences and Harvard Medical School, and co-corresponding author on a paper reporting the research in Cell Stem Cell.

“It’s very important for the research community to learn that targeting the AXL protein alone will not defend against Zika,” agreed Ajamete Kaykas, co-corresponding author and a senior investigator in neuroscience at the Novartis Institutes for Biomedical Research (NIBR).

Previous studies have shown that blocking expression of the AXL receptor protein does defend against the virus in a number of human cell types. Given that the protein is highly expressed on the surface of NPCs, many labs have been working on the hypothesis that AXL is the entry point for Zika in the developing brain.

“We were thinking that the knocked-out NPCs devoid of AXL wouldn’t get infected,” said Max Salick, a NIBR postdoctoral researcher and co-first author on the paper. “But we saw these cells getting infected just as much as normal cells.”

Working in a facility dedicated to infectious disease research, the scientists exposed two-dimensional cell cultures of AXL-knockout human NPCs to the Zika virus. They followed up by exposing three-dimensional mini-brain “organoids” containing such NPCs to the virus. In both cases, cells clearly displayed Zika infection. This finding was supported by an earlier study that knocked out AXL in the brains of mice.

“We knew that organoids are great models for microcephaly and other conditions that show up very early in development and have a very pronounced effect,” said Kaykas. “For the first few months, the organoids do a really good job in recapitulating normal brain development.”

Historically, human NPCs have been difficult to study in the lab because it would be impossible to obtain samples without damaging brain tissue. With the advancements in induced pluripotent stem cell (iPS cell) technology, a cell reprogramming process that allows researchers to coax any cell in the body back into a stem cell-like state, researchers can now generate these previously inaccessible human tissues in a petri dish.

The team was able to produce human iPS cells and then, using gene-editing technology, modify the cells to knock out AXL expression, said Michael Wells, a Harvard postdoctoral researcher in the Eggan Lab and co-first author. The scientists pushed the iPS cells to become NPCs, building the two-dimensional and three-dimensional models that were infected with Zika.

The Harvard and NIBR collaborators started working with the virus in mid-April 2016, only six months before they published their findings. This unusual speed of research reflects the urgency of Zika’s global challenge, as the virus has spread to more than 70 countries and territories.

“At the genesis of the project, my wife was pregnant,” Eggan remarked. “One can’t read the newspapers without being concerned.”

The collaboration grew out of interactions at the Broad Institute of Harvard and MIT’s Stanley Center for Psychiatric Research, where Eggan directs the stem cell program. His lab already had developed cell culture systems for studying NPCs in motor neuron and psychiatric diseases. The team at Novartis had created brain organoids for research on tuberous sclerosis complex and other genetic neural disorders.

“Zika seemed to be a big issue where we could have an impact, and we all shared that interest,” Eggan said. “It’s been great to have this public/private collaboration.”

The researchers are studying other receptor proteins that may be open to Zika infection in hopes that their basic research eventually will help in the quest to develop vaccines or other drugs that defend against the virus.

See the full article here .

YOU CAN HELP FIND A CURE FOR THE ZIKA VIRUS.

There is a new project at World Community Grid [WCG] called OpenZika.
Zika
Zika depiction. Image copyright John Liebler, www.ArtoftheCell.com
Rutgers Open Zika

WCG runs on your home computer or tablet on software from Berkeley Open Infrastructure for Network Computing [BOINC]. Many other scientific projects run on BOINC software.Visit WCG or BOINC, download and install the software, then at WCG attach to the OpenZika project. You will be joining tens of thousands of other “crunchers” processing computational data and saving the scientists literally thousands of hours of work at no real cost to you.

This project is directed by Dr. Alexander Perryman a senior researcher in the Freundlich lab, with extensive training in developing and applying computational methods in drug discovery and in the biochemical mechanisms of multi-drug-resistance in infectious diseases. He is a member of the Center for Emerging & Re-emerging Pathogens, in the Department of Pharmacology, Physiology, and Neuroscience, at the Rutgers University, New Jersey Medical School. Previously, he was a Research Associate in Prof. Arthur J. Olson’s lab at The Scripps Research Institute (TSRI), where he ran the day-to-day operations of the FightAIDS@Home project, the largest computational drug discovery project devoted to HIV/AIDS, which also runs on WCG. While in the Olson lab, he also designed, led, and ran the largest computational drug discovery project ever performed against malaria, the GO Fight Against Malaria project, also on WCG.

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The Harvard Medical School community is dedicated to excellence and leadership in medicine, education, research and clinical care. To achieve our highest aspirations, and to ensure the success of all members of our community, we value and promote common ideals that center on collaboration and service, diversity, respect, integrity and accountability, lifelong learning, and wellness and balance. To be a citizen of this community means embracing a collegial spirit that fosters inclusion and promotes achievement.

Harvard University campus

Harvard is the oldest institution of higher education in the United States, established in 1636 by vote of the Great and General Court of the Massachusetts Bay Colony. It was named after the College’s first benefactor, the young minister John Harvard of Charlestown, who upon his death in 1638 left his library and half his estate to the institution. A statue of John Harvard stands today in front of University Hall in Harvard Yard, and is perhaps the University’s best known landmark.

Harvard University has 12 degree-granting Schools in addition to the Radcliffe Institute for Advanced Study. The University has grown from nine students with a single master to an enrollment of more than 20,000 degree candidates including undergraduate, graduate, and professional students. There are more than 360,000 living alumni in the U.S. and over 190 other countries.

#applied-research-technology, #harvard-medical-school, #medicine, #openzika-project-at-world-community-grid, #zika

From Rutgers: SWomen in STEM: “Zika and Water Safety Education a Mission for Rutgers Alumna” Amber Gourdine

Rutgers University
Rutgers University

10.3.16
Patti Verbanas

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Amber Gourdine, shown with members of the community she served, spent hours each day walking to residences to examine filtration systems, assess residents’ knowledge about water sanitation and educate them about Zika. Photo: Courtesy Amber Gourdine

Amber Gourdine wasn’t taking any chances.

Braving the humid, 90-degree days in central Nicaragua, the recent Rutgers graduate donned long sleeves and tucked her pants into her socks to avoid mosquito bites. Then, she embarked on daylong hikes to rural homes to educate residents on water safety and how to protect themselves against the Zika virus, which is on the rise throughout most of the country.

“I sprayed Permethrin and Off on my clothes and used mosquito nets, but despite my best attempts, I got bitten,” says Gourdine, who spent nine weeks this summer serving in the global health intensive program at AMOS Health and Hope, a nonprofit that works in impoverished Nicaraguan communities to improve citizens’ health through education and development projects. “That’s why education is so important – reducing mosquitos and taking precautions by eliminating standing water and proper hygiene is the best defense.”

Although the incidence of Zika has fallen in many Central American countries, Nicaragua and Costa Rica are still reporting increases, according to the Pan American Health Organization. In August, Nicaragua confirmed its first microcephaly birth linked to Zika.

Gourdine was part of a rapid response to the Zika outbreak by the Nicaraguan government, which relies on organizations like AMOS to teach remotely located residents how the virus spreads and ways to prevent mosquito breeding grounds.

Gourdine, who graduated in May with a bachelor’s of science degrees in public health and in arts and sciences, learned about AMOS during an on-campus information session in New Brunswick, where she was enrolled at Douglass Residential College. “It excited me because it would allow me to put my interest in public health education into action,” she says.

As part of AMOS’s clean water team, Gourdine’s mission was to educate the rural community on safe water practices and daily hygiene to help stem water-borne diseases. The Zika education is a new component AMOS added this year to the team’s mission.

Joining three colleagues and a supervisor, she spent hours each day walking from their home base to residences sprinkled throughout the countryside to examine water filtration systems AMOS had installed, assess the residents’ knowledge about water sanitation and educate them about Zika.

Zika is the latest public health threat in the communities AMOS serves, where less than 20 percent of the families have access to safe drinking water. To date, the organization has installed more than 1,000 water filters and relies on volunteers like Gourdine to make sure the residents know how to use and maintain the systems.

“It was eye-opening how little people knew about Zika,” says Gourdine, whose Spanish studies allowed her to speak to residents without a translator. “Many knew the name and that the virus was spread by mosquitos, but few knew it could be sexually transmitted. Before I left each home, I put an informational poster on the wall.”

Gourdine also assisted with teaching residents about water sanitation and trash disposal. “Waste management is a huge issue,” she says. “Since the houses are so spread apart, there is no trash collection. Instead of burning or burying trash, people leave it to decay in the yard, where it becomes a breeding ground for mosquitos.”

2
Amber Gourdine shown here demonstrating proper hygiene to community members.

The AMOS mission was Gourdine’s second visit to the country since graduation. In late May, she joined the Rutgers Global Brigade for a week of building latrines, installing septic tanks and educating residents on healthy habits. Originally, she considered pursuing nursing, but she became intrigued with public health after taking a course sponsored by Rutgers at Academica Latinoamericana de Español in Peru in 2014 as part of her Spanish studies. While there, she researched local women’s public health issues, such as domestic violence and HIV/AIDs, and presented the report to the faculty at the school.

Upon completing her work in Nicaragua in August, Gourdine returned to her home in Magnolia, New Jersey, where she aspires to work with Americorps as a community health coordinator and eventually apply to graduate school.

“Public health is fascinating because you have to view a population the same as the patient: Just as a patient knows more about their bodies and themselves than a doctor, a community of people know more about their own issues in ways more than an outsider would,” she says. “I love the mutual exchange of ideas with community members to resolve health issues together.”

See the full article here .

YOU CAN HELP FIND A CURE FOR THE ZIKA VIRUS.

There is a new project at World Community Grid [WCG] called OpenZika.
Zika
Zika depiction. Image copyright John Liebler, www.ArtoftheCell.com
Rutgers Open Zika

WCG runs on your home computer or tablet on software from Berkeley Open Infrastructure for Network Computing [BOINC]. Many other scientific projects run on BOINC software.Visit WCG or BOINC, download and install the software, then at WCG attach to the OpenZika project. You will be joining tens of thousands of other “crunchers” processing computational data and saving the scientists literally thousands of hours of work at no real cost to you.

This project is directed by Dr. Alexander Perryman a senior researcher in the Freundlich lab, with extensive training in developing and applying computational methods in drug discovery and in the biochemical mechanisms of multi-drug-resistance in infectious diseases. He is a member of the Center for Emerging & Re-emerging Pathogens, in the Department of Pharmacology, Physiology, and Neuroscience, at the Rutgers University, New Jersey Medical School. Previously, he was a Research Associate in Prof. Arthur J. Olson’s lab at The Scripps Research Institute (TSRI), where he ran the day-to-day operations of the FightAIDS@Home project, the largest computational drug discovery project devoted to HIV/AIDS, which also runs on WCG. While in the Olson lab, he also designed, led, and ran the largest computational drug discovery project ever performed against malaria, the GO Fight Against Malaria project, also on WCG.

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Rutgers, The State University of New Jersey, is a leading national research university and the state’s preeminent, comprehensive public institution of higher education. Rutgers is dedicated to teaching that meets the highest standards of excellence; to conducting research that breaks new ground; and to providing services, solutions, and clinical care that help individuals and the local, national, and global communities where they live.

Founded in 1766, Rutgers teaches across the full educational spectrum: preschool to precollege; undergraduate to graduate; postdoctoral fellowships to residencies; and continuing education for professional and personal advancement.

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For WCG From Orlando Sentinel

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World Community Grid (WCG)

1

Orlando Sentinel

9.10.16
Kate Santich

If you knew you could fight Zika by downloading an app, would you?

In the battle against Zika, Danny Leoni of Casselberry has been called a superhero. Night and day, the 26-year-old is running algorithms to find the chemical compounds that could deactivate the virus and offer a cure.

But don’t look for his name in the Nobel Prize nominations anytime soon. He is simply lending the spare capacity of his computer.

“I figured, ‘Hey, it’s something actually useful instead of being on Netflix for eight hours at a time,'” he says.

Leoni is a volunteer for the nonprofit Hands On Orlando, which has recruited nearly 1,000 people whose computers, tablets and phones act as a collective supercomputer for researchers around the globe.

“The beauty of it is, you don’t have to have any particular skills. You don’t have to have any scientific background. You just have to care,” says Chris Allen, executive director of Hands On Orlando, which matches volunteers to group projects — such as sorting donations at food banks or washing dogs at pet shelters.

But for eight years, Allen’s nonprofit organization also has enlisted participants for what he dubbed the Super Heroes team.

Together they run scientific calculations that have led to advances in solar energy, treating childhood cancer and fighting AIDS. All volunteers need to do is download an app that allows their computers and phones to process data.

The app comes from the World Community Grid — an award-winning philanthropic project of IBM Corporate Citizenship, the tech company’s social responsibility initiative. For anyone worried that getting involved would open their devices to hackers, IBM is quick to point out that it installs the app on its own employees’ computers.

“As you can imagine, we take security very, very seriously,” says Juan Hindo, the World Community Grid program manager. “So we have all kinds of security measures in place. … It doesn’t touch any of the private data on your device.”

Since the project’s launch, researchers have used the grid to run massive computer simulations involving billions of variables by breaking up the data into personal computer-sized morsels that can run in the background as long as your device is turned on and connected to the internet.

The work, researchers report, has led to progress in fighting malaria, tuberculosis, muscular dystrophy, cancer and influenza. It has spurred the development of filtration systems for clean water and rice that has higher crop yields and more protein. And it is helping to map climate change.

But the Super Heroes’ most recent work has been on OpenZika, a project by an international team of scientists searching for a critically needed anti-viral drug to combat the disease. Currently, there is none.

Leoni, an aspiring web developer who joined the team a year and a half ago, says that project and another on cancer inspired him to sign up.

“Several people in my family have had cancer,” he says. “To know I’m contributing to the research definitely makes me feel good. Although I admit — the whole thing still blows my mind a little bit.”

Though the Super Heroes team ranks No. 224 out of nearly 32,600 teams participating worldwide, both Allen and Hindo acknowledge the potential is still largely untapped. The biggest hurdle, they say, is that most people just don’t understand it.

“A typical researcher, if they’re lucky, might have access to a supercomputer a few weeks a year — and then they’re sharing with dozens of other researchers on campus,” Hindo says. “And because there’s a very difficult funding climate for scientific researchers, they don’t want to spend a lot of their money on computer time, so they end up scaling down the scope of their research.”

But by distributing the load through thousands of volunteers worldwide, each researcher can have the equivalent of his or her own small supercomputer for as long as necessary, 24 hours a day, Allen says.

More than 720,000 people around the world have joined the effort so far.

In the Hands On office alone, 16 computers are enlisted. Kyle Trager, the community partnerships manager there, also has the app on his phone and his computer at home.

“You don’t even know it’s running,” he says. “I just plug in my phone to charge overnight, and once it gets to 90 percent, it’ll crunch these calculations.”

There’s never a slowdown of processing, Allen insists. And if the charity’s power bill went up as a result, it wasn’t noticeable.

“The benefit of joining our team [handsonorlando.com/superheroes] is that you can call us and we will help you set it up,” he says. “And when scientists find a drug for Zika or a cure for cancer, you can say you helped make it happen.”

See the full article here.

YOU CAN HELP FIND A CURE FOR THE ZIKA VIRUS.

There is a new project at World Community Grid [WCG] called OpenZika.
Zika
Zika depiction. Image copyright John Liebler, www.ArtoftheCell.com
Rutgers Open Zika

WCG runs on your home computer or tablet on software from Berkeley Open Infrastructure for Network Computing [BOINC]. Many other scientific projects run on BOINC software.Visit WCG or BOINC, download and install the software, then at WCG attach to the OpenZika project. You will be joining tens of thousands of other “crunchers” processing computational data and saving the scientists literally thousands of hours of work at no real cost to you.

This project is directed by Dr. Alexander Perryman a senior researcher in the Freundlich lab, with extensive training in developing and applying computational methods in drug discovery and in the biochemical mechanisms of multi-drug-resistance in infectious diseases. He is a member of the Center for Emerging & Re-emerging Pathogens, in the Department of Pharmacology, Physiology, and Neuroscience, at the Rutgers University, New Jersey Medical School. Previously, he was a Research Associate in Prof. Arthur J. Olson’s lab at The Scripps Research Institute (TSRI), where he ran the day-to-day operations of the FightAIDS@Home project, the largest computational drug discovery project devoted to HIV/AIDS, which also runs on WCG. While in the Olson lab, he also designed, led, and ran the largest computational drug discovery project ever performed against malaria, the GO Fight Against Malaria project, also on WCG.

Rutgers smaller

Please help promote STEM in your local schools.
STEM Icon

Stem Education Coalition

World Community Grid (WCG) brings people together from across the globe to create the largest non-profit computing grid benefiting humanity. It does this by pooling surplus computer processing power. We believe that innovation combined with visionary scientific research and large-scale volunteerism can help make the planet smarter. Our success depends on like-minded individuals – like you.”

WCG projects run on BOINC software from UC Berkeley.
BOINCLarge

BOINC is a leader in the field(s) of Distributed Computing, Grid Computing and Citizen Cyberscience.BOINC is more properly the Berkeley Open Infrastructure for Network Computing.

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CAN ONE PERSON MAKE A DIFFERENCE? YOU BET!!

MyBOINC

“Download and install secure, free software that captures your computer’s spare power when it is on, but idle. You will then be a World Community Grid volunteer. It’s that simple!” You can download the software at either WCG or BOINC.

Please visit the project pages-

FightAIDS@home Phase II

FAAH Phase II
OpenZika

Rutgers Open Zika

Help Stop TB
WCG Help Stop TB
Outsmart Ebola together

Outsmart Ebola Together

Mapping Cancer Markers
mappingcancermarkers2

Uncovering Genome Mysteries
Uncovering Genome Mysteries

Say No to Schistosoma

GO Fight Against Malaria

Drug Search for Leishmaniasis

Computing for Clean Water

The Clean Energy Project

Discovering Dengue Drugs – Together

Help Cure Muscular Dystrophy

Help Fight Childhood Cancer

Help Conquer Cancer

Human Proteome Folding

FightAIDS@Home

World Community Grid is a social initiative of IBM Corporation
IBM Corporation
ibm

IBM – Smarter Planet
sp

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