 Okay. Thank you, Mark. So I have a usually detailed director's report prepared by various members of the staff. So we do have a lot of ground to cover. I did thought it was probably important to start off by just marking the moment yesterday, obviously with the 10th anniversary of the 9-11 tragedies. I'm sure all of you reflected on where you were when those horrible events occurred 10 years ago. I can tell you at a personal level, I was sitting in the office of my laboratory meeting with various members of my lab on that day and would seem like a very calm morning at NIH. Interestingly, there's some important history associated with this council in 9-11 because just a two-minute walk from where I was sitting in my lab office was the Natural Conference Center, which is where council used to meet and they were convened on day two of their September meeting. I'm told that when all this happened, Francis Collins was handed a note or somehow was told the information about the events and shortly thereafter the meeting ended abruptly. I will also tell you many council members were stranded here in the area for multiple days to follow. So from our collective sanity, I'm just hoping nobody comes up to me and passes a note or whispers in my ear anything for the next two days. I don't need that to happen. Actually, Eric, can I make a slight correction on that? What was that? And that is Francis was actually out of the room. He was out of the room for conflict reasons. He was the one who came back and told us about it. Well, so it was a bizarre time. So I just thought it was important to remind us of that history. So the open session of council is being webcast live as we are going to continue to do in the future and we also will make web archives available of the open session and all of its documents. For new council members and also for our ad hoc members or people who haven't been at council for a while notice some things are different. I just want to make you aware there is an electronic resource that's associated with my director's report. It's sort of like a supplemental material section for a published paper and the URL that you can find all this material that is shown on the slide. My slides are also available electronically both as a PowerPoint file and also as a PDF file. And for slides that are associated with relevant documents or websites, we indicate that with a document number shown on the bottom right. And this entire site including all link documents will be permanently archived on the NHGRI website for future reference and we do know that people access this information. You're welcome to do so. I'm going to cover the usual seven areas, these indicated areas during my director's report. This has proven to be a very good framework to cover all the things I want to cover. Now, in addition to my director's report, there's going to be other presentations in the open session of council. And so I've tailored my director's report around these presentations, meaning that I'll touch lightly on those topics since others will be covering them in the open session. The talk after mine will be given by Laura Rodriguez describing the NHGRI Office of Policy Communication and Education. And then the next presentation will be on a meeting report about the Chicago Genomics Meeting, a Genomic Medicine Meeting, Terry Monoglio and Jeff Ginsberg from council will be jointly making that presentation. We then have three program updates that we want to give you in greater detail. Two on the Common Fund, one on NHGRI program. Jane Peterson will be updating you about the H3Africa project. Jeff Struing will be updating you about the G-TEX project. These are both Common Fund projects. And then as a prelude to what we're going to talk about extensively in closed session, Adam Felsenfeld is going to give an overview of NHGRI's large scale genome sequencing program. So that's what we have in store in terms of presentations during the open session. So let me just jump in and start first with some general NHGRI updates. And I guess we should start with nature, not the journal, but nature itself. We've had more episodes of nature's wrath. Remember last year I updated you how we had blistering heat and power outing winds that occurred over the summer. And we even had a teeny, teeny little earthquake about a year ago. But this year we had the real thing just a few weeks ago. I didn't feel it. I was actually in my car pulling into the garage at Twinbrook right here. I didn't even know it had happened. But there was some minor damage on and off campus. You'll see the 12A, how the A is falling out. That's on the NIH campus. That's one of the more visible bits of damage we had. But you can see also shown in the slide is what happened at the National Cathedral downtown and also shown in the bottom right are some of the cracks in the Washington Monument that are now there because of the earthquake. So after the earthquake hit, we had a few days off and we collected our brass and then we were hit with Hurricane Irene. And it was rained and rained and rained. And actually last week was even worse than the actual hurricane itself. Now in some ways I just think that these two natural disasters were just a test of our emergency preparedness for the next disaster that'll be faced. And that's of course the upcoming budget showdown. But I'll give you more about that a little bit later. Significant NHGRI updates. Let me start here more seriously with this important update which all of you should have gotten emailed about last week or we made public last week. Mark Geyer is now the deputy director of NHGRI. Since he was hired as employee number four in 1988 he's had a long and wonderful career at this institute. Almost a decade now serving as the director of the extramural program. I remember that he was my acting deputy director since I became director in December 2009 and now he'll simply flip his acting titles. He will be the deputy director of the institute and the acting director of our extramural program while longer term leadership plans are formulated. As mentioned during the staff introductions, Dr. Derek Scholes recently joined NHGRI as the new chief of our policy and program analysis branch within our office of policy communications and education. Derek received his doctoral training at the University of Liverpool and then went to Albany, New York for post-doctoral training at the Wasworth Center. He's an alumnus of this NHGRI American Society of Human Genetic Public Policy Fellowship program. You just heard and were introduced to our newest member, Kristina Kapusti. And as an alumnus of that program, while he was in the program he spent some time at NHGRI and a few months within the branch that he now heads but then went off and did a year-long stint in the late Senator Edward Kennedy's office. He comes to us most directly from the American Heart Association where he advocated for legislation supporting health and biomedical research including significant contributions to see GINA pass and to help implementing the regulations as they got drafted as well as substantial work on family smoking prevention and tobacco control act. Flipping over to our intramural program earlier this summer Dr. Paul Lu was named the NHGRI Deputy Scientific Director by Dan Kastner, our scientific director. Dr. Lu is a tenured senior investigator. He came to NIH and NHGRI a year before I did, actually in 1993 at the inception of our intramural program. And he's a world expert in the onset development and progression of leukemia. Dr. Lu also heads the oncogenesis and development section within our genetics and molecular biology branch. The deputy scientific position actually became available because our previous and long-standing Deputy Scientific Director Andy Box-Avonix accepted a new NIH-wide position in the NIH Office of Intramural Research which is headed by Michael Goddisman. And in this new position Andy will provide leadership in the area of bioinformatics and information technology for the entire NIH intramural program. But in addition he'll continue to have his affiliation with NHGRI where he'll continue his research role in directing our bioinformatics core. Along with the announcement last week about Mark Geier we also announced the appointment of Jim Mulligan as Director of the NIH Intramural Sequencing Center. Jim is an outstanding genomics researcher bringing many years of high-level experience to this position starting at the Sanger Institute and now for many years at NHGRI. I took a lot of interest in this search and eventual appointment of Jim as the person who originally founded NISC in 1997. I was the Director for over 12 years. When I had a hand over the acting Director Reigns I was very comfortable doing this though by having Jim take over as Acting Director since December 2009 and now I'm really delighted to see him selected by Dan Castan to be NISC's permanent Director. Vivian Oda-Wong who's a Program Director and Extramural Research Program was elected a Fellow in the American Psychological Association. Fellow status is an honor bestowed upon members of this association who have shown evidence of unusual and outstanding contributions or performance and it requires evidence of national impact on the field of psychology. So congratulations Vivian. Now there are two special advisors that are now on board at NHGRI. Both have been mentioned at previous Council meetings and I just wanted to give you little updates about both. The first is Karen Rothenberg who is here sitting in the front row. Karen is taking a one-year sabbatical from the University of Maryland Law School to work full-time at NHGRI. She's working jointly at NHGRI and also the Department of Bioethics in the NIH Clinical Center and during this year she has multiple projects that she'll be pursuing. One of which is to lead an effort to take a rigorous and thoughtful examination of our LC program and other NHGRI components that will expand and integrate into the vision for genomics and society as described in our recently published strategic plan. Second thing she's going to be involved in is working with colleagues here to co-author some scholarly papers in areas such as regulation of genomic research and the return of research results and incidental findings encountered in whole genome sequencing studies. And third effort will be exploring how theater vignettes can enhance our understanding of LC issues in genetics and innovation in science. So we're happy that Karen is on board and sitting just a couple seats a little bit back and a couple seats over from her is my other special advisor, Mark Williams who's also here spending about a week a month at NHGRI as a special advisor in the area of genomic medicine. Mark's director of the Intermountain Health Care Clinical Genetics Institute in Salt Lake City among his various efforts with us, Mark is particularly active in working to help us enhance our programs related to genomics and electronic health records as well as the development of clinical genomics information systems. And for the latter, he's actually going to be co-chairing a workshop in December that I'll be mentioning later in my talk. I would encourage you during the breaks to talk to either or both of them. They'll be around during the open session of council and we're delighted to have both of them on board and they're proving to be very helpful to me. So moving beyond NHGRI, many things are changing. In fact, lots of deck chairs are getting rearranged that seems at NIH. So let me run through the major announcements in that area. So Dr. Martha Somerman has now arrived as the new director of the National Institute of Dental and Craneo-Facial Research. She previously was the dean at the University of Washington School of Dentistry, a position that she's held since 2002 before coming to NIH. She's an internationally known research and educator and her research has focused on defining the key regulators controlling development, maintenance and regeneration of oral, dental and cranial facial tissues. Major changes at the National Institute of General Medical Sciences. As you know, Jeremy Berg recently departed as director. Judith Greenberg is now in place as the acting director of the National of this Institute. She's a developmental biologist and director of the NIGMS Division of Genetics and Developmental Biology since 1988. I should point out that this division that she heads has an annual budget of $566 million, which is bigger than NHGRI in budget. So she's terrifically qualified to be an acting director. And she's actually served previously as acting director for May of 2002 until November of 2003. She will not have a long stint in this acting role because Dr. Chris Kaiser, who is currently the chairman of biology at MIT, has been selected to be the next director of NIGMS, pending final approvals, which are being sought. I happen to know Chris Well, besides both of us being born in St. Louis, about a year apart, although I didn't know him back then. Our career paths have actually overlapped in various ways over the years. He's an outstanding yeast biologist and a well regarded scientific leader at MIT. Some of his references included people we know very well in the Cambridge area. I happen to know a little bit more about that because he served on the search committee and it was really just outstanding that we were able to identify someone of his caliber and convince him to come here. And we're expecting, assuming all approvals come in, that he'll be starting at the helm of NIGMS April 1st of next year. And in fact, we're already having discussions with him about ways to consider enhanced interactions between our institute and NIGMS. Also, significant changes of foot for the National Center for Research Resources and NCRR. Barbara Alvin, who's currently the director, will be leaving NIH at the end of the month. She's been director of the NCRR since 2007. Previously she served as the deputy and then acting director of the National Heart, Lung and Blood Institute and also headed the women's health initiative before she came to NCRR. Incoming acting director is Dr. Louise Ram, who's now the deputy director and the director of extramarital activities for NCRR. And she's agreed to be the acting director of NCRR starting October 1. Now, Dr. Ram received her PhD in microbiology at the University of Virginia in 1974. She's a faculty member at Johns Hopkins and the microbiology department. She joined NCRR in 1987 as a health scientist administrator in the biological models materials program and subsequently became director of that program in 1994. Of course, the interesting thing about NCRR is that it is proposed for NCRR to go away around October 1 or shortly thereafter and we'll get to this more when we talk about the proposed National Center for Advancing Translational Sciences where a major section of NCRR will move into. And so this is all very much transitional issues waiting for some of the proposed reorganizational things that are making their way through the legislative approvals. But that's the current state of affairs for NCRR. It's also major changes in the Center for Scientific Review. Dr. Tony Scarpa is departing the directorship of that center later this month and he's held that position since 2005. During his tenure there, Dr. Scarpa implemented the trans-NIH Enhancing Peer Review changes which included the new scoring system. He also saw NIH through the review of 40,000 American Recovery and Reinforcement Act applications two years ago. Following Dr. Scarpa's departure and while NIH conducts a national search for a new director, Dr. Richard Nakamura will serve as acting director of CSR. Dr. Nakamura has served in leadership positions at the National Institute of Mental Health, multiple different leadership positions. He has been the scientific director most recently. Prior to that he was the deputy director. He was also acting director of the institute from 2001 to 2002. At the NIH Center for Information Technology in October, Andrew Norris will become this center's new director. She will also be the acting chief information officer of NIH. Ms. Norris comes from the National Science Foundation, having been there for 10 years and most recently as the acting chief information officer and director of the organization responsible for providing agency-wide information technology systems, services, and supporting infrastructure. Going over to the National Cancer Institute, Dr. Barbara Wold has begun her stint as interim director for NCI Center for Cancer Genomics while she takes a sabbatical from her appointment at Caltech. Dr. Wold, who's familiar to many of us, is the brand professor of electrobiology and director of the Beckman Institute at Caltech. She's obviously served on numerous advisory roles. For NHGRI is also one of our grantees. There's sad news that occurred over the summer. A couple of things to report. Dr. Bernadine Healy, former director of the NIH, passed away in August. During her tenure and as the first female NIH director, Dr. Healy started the Women's Health Initiative. She also recruited Frances Collins to come lead the NHGRI and she was the one that helped create the NHGRI Intramural Research Program. She also ran the Red Cross in the late 1990s. Another sad announcement that Senator Mark Hatfield, who is a visionary supporter of medical research, passed away in August, in fact the same week. As chair of the Senate Committee on Appropriations, he served as a strong and principled advocate for the needs of those who are less fortunate. He also consistently defended the importance of NIH-funded research and its importance in our society. I should point out, and I think very appropriately, you should realize that the NIH Clinical Center is actually bears his name. It's the Mark Hatfield Clinical Research Center and commemorating his contributions to NIH. As part of ongoing effort to examine and improve the diversity of the scientific workforce, NIH has actually commissioned several different studies to look at this problem. One such study was led by former NIH Deputy Director Rainer Kington and that was recently published in Science. This study, and just in brief, analyzed the probability of securing first-time NIH R01 funding looking at the period 2000 to 2006 and they looked at the probability based on race and ethnicity controlling for observable characteristics such as NIH training, research experience, and institution. But even after controlling for all those factors that might influence the likelihood of success, black applicants were found to be 10% less likely than white applicants to receive Type 1 R01 award. Very concerning. And in the same issue of science, Drs. Tabeck and Collins provided a perspective piece that outlines NIH commitment to a diverse biomedical workforce and future plans to address this issue. The U.S. Department of Health and Human Services has now issued a final rule that amends the public health service regulations on, quote, responsibility of applicants for promoting objectivity and research for which PHS funding is sought and responsible prospective contractors. This is a word, a big mouthful, basically talking about financial conflict of interest, especially for those in the extramural program. It's actually a revision of the 1995 guidelines and reflects a tightening of the rules. And there are major changes to previous policy that if you're not aware of, I would encourage you to become aware of. It includes lowering the monetary threshold at which significant financial interests require disclosure, generally from about 10,000 to 5,000. Requires investigators to disclose to their institutions all of their significant financial interests related to their institutional responsibilities. Requires institutions to report to NIH additional information on identified financial conflicts of interest and how they are being managed. Requires institutions to make certain information accessible to the public concerning identified significant financial interests held by senior and key personnel. And requires investigators to complete training related to the regulations and their institutions financial conflict of interest policy. Of course, the reason you want to become familiar with this is that the implementation of this new policy will occur no later than August 24th of next year. And I'm sure you're hearing about this at your local institutions. I think this is being taken very seriously as it should. Moving on, a key flagship component of Francis Collins' plans for NIH as director is to establish this proposed National Center for Advancing Translational Sciences, or NCATS. I alluded to earlier related to the closing of NCRR and the movement of programs within NCRR to new homes. Well, there's been considerable effort within NIH to formulate the plans for creating this new center and considerable reactions, both positive and negative, in the scientific community about the creation of this center. There is now a formulated mission statement for this proposed center to advance the discipline of translational science and catalyze the development of testing of novel diagnostics and therapeutics across a wide range of human diseases and conditions. Now, as you may be hearing about or you may have read about, this is complicated, especially in the current political climate where this was supposed to be created at the beginning of next fiscal year. But we likely won't have a budget at the beginning of the next fiscal year, and yet there is a whole choreography that must take place in order for all of this to happen. Just briefly, let me just tell you so you know what is thought to happen. The most likely scenario at the moment for creating NCATS next fiscal year, hopefully early in the fiscal year, in the face of a continuing resolution, which is basically continued business as it was last year at the funding levels of last year, because that's likely what we'll have, will be what is called an anomaly, which is basically wording that is put into the continuing resolution that says everything was before with the following anomalies, and then they can list things that are different. And the hope is that wording to create NCATS will be put as an anomaly and this is required, I'm sure, hundreds of hours of leadership time Francis and others to make this happen. And so it is hopeful that will happen. And so in anticipation that NCATS is going to be created in the coming months, maybe weeks, but hopefully months. In fact, the search committee for its director has now begun its work. I know about this because I'm actually co-chair of the search committee along with Tom Insel, the director of NIMH. And so first thing I would say is if you know of good candidates, possibly you'd be interested in running this flagship new component of the NIH, hopefully once it gets created. Please let me know. The search committee is active and Francis is extremely anxious for us to identify somebody so that when it does get created, shortly thereafter we would have a director in place. There are also implications of the creation of NCATS for NHGRI, as a reminder the National Center for Translational Therapeutics, which houses within it the NIH Center for Chemical Genomics. All entities you've heard a little bit about in the past, Chris Austin is now the scientific director of that entire enterprise. It's grown up within NHGRI for about the past nine or 10 years, but it will depart in block completely to NCATS when NCATS gets created, taking with it about over 100 employees of NHGRI. We'll be moving into NCATS as part of that transfer. Now if you want to know more about NCATS and the proposed new center, the blueprint for it was written up by Francis and published in Science Translational Medicine, and that's available in document 11. I would encourage you to look at that if you're not familiar with some of the details of what Francis sees for this new center. Okay, now to the really tricky part of director's report. Fiscal year 2012 appropriations. It's so complicated I had to go to a smaller font to fit it in because I have so much to tell you. So, and I figured you're probably very interested in this. So we're currently in fiscal year 2011 operating with a budget that was signed by the president April amid imminent threats of a government shutdown. The budget reflects a 1% reduction compared to last year. A reminder that's the first such reduction that NIH had seen in many, many years. It provided NIH with $30.9 billion in NHGRI with $511 million. Now, since fiscal year 12 begins October 1, you might have naively expected that Congress would have completed its passage of legislation to fund the government for next year, but as you well know, congressional agreement on funding the government is rarely straightforward and the debate this year is particularly complex because of the recent, shall we say, situation with the debt deal. And I'll move on to say about the debt deal on the next slide, but here's where we're at. The president's fiscal 12 budget requests $32 billion for NIH and $535 million for NHGRI, a 2.4 and 1.7% increase over the current fiscal year respectively. Now, at this point in time, such an increase seems extremely unlikely considering the larger set of complex circumstances. So Congress needs to pass a number of bills to fund the government. To give you a flavor, so far the house has passed six of 12 such bills, three are out of committee, including the one we care about and the others and three are without... Oh, no, three are out of committee and three including the one that we're most interested in are without action. The Senate is doing worse. They've only passed one of 12 bills, three are out of committee and eight are without action. And the one we're most interested in which sets the funding levels for NIH is the one crafted by the Labor HHS and Education and Related Agencies Appropriations Subcommittee in the House and Senate sort of known as the Labor HHS Bill. Neither House nor Senate has passed the Labor HHS Bill this year and even debated draft legislation. So at this point in time, we don't even know what the funding levels for NIH or NHGRI will be. Now, it's unlikely that Congress will pass appropriations bills by the end of this month. So you're most surely looking towards a continuing resolution to keep the government functioning in the interim until a final agreement is reached for the rest of the year. The most likely scenario at this point is a continued resolution for authorizing operations through the holidays or the way through the system. Well, predictions about NIH funding are quite varied depending upon who you ask and when you ask. It would seem the best case would be flat. The most realistic case is something like minus 2 percent and the worst case being something like minus 5 percent. What I would tell you is in the meantime, please keep your seatbelts buckled because this is going to be a wild and turbulent ride for the next few months. And the real elephant in the room in terms of appropriations, of course, and the reason why Congress has not yet completed its appropriations work is the strong disagreement among congressional members regarding the role and size of the government programs. This most recently manifested as the debate over the size of the government debt that had not been temporarily resolved would have led to the government defaulting on its debt for the first time in history. As you know, a debt deal was struck at the 11th hour and the default was avoided in a dramatic fashion. But the not-so-good news for all this is that the terms of the deal are almost certainly to affect NIH funding in a bad way for several years to come. So the so-called debt deal comes in two parts. One part is a cap on the total funds that Congress can appropriate for each year going forward through the next decade. The debt deal only sets a cap on total spending across the government and so there's no reason to assume that all agencies will be equally impacted. It's really difficult to predict how NIH may fare compared with other agencies but it's clear that all budgets will be under extreme pressure. Part two of the debt deal established a joint select committee on deficit reduction, more commonly referred to as the super committee, to identify additional ways to reduce the federal deficit. So by November 23rd the group is charged with crafting a bill that reduced the deficit by at least $1.2 trillion by 2021 and to ideally identify up to $1.5 trillion in total reductions. Each chamber of Congress must then be required through a simple up and down vote to approve the super committee proposal by December 23rd. The committee's proposal may include reductions in spending such as further reductions to agency funding or entitlement programs and increased revenues through changes in the tax code, for example. Well, a very important detail is what happens if the super committee fails to come upon a proposal that they all agree to and if Congress does not pass the proposal by the end of the year, a failure at either would trigger the across the board cuts to federal agencies in 2013 to equal the $1.2 trillion they were supposed to have identified and this substantial degree of cuts will likely have a significant effect on the NIH if it's a simple trigger. Well, the debt ceiling agreement is not expected to substantially diminish 2012 funding and, like I said, most likely scenarios flatter minus 2% because it well may result in significant cuts in 2013 and beyond. In fact, we're being asked to prepare various scenarios for 2013 that include cuts of 5% and also cuts of 10%. It was interesting this morning when I was driving here and I had on the radio it was the first time I had heard an advertisement sponsored by AAMC the American Association of Medical Colleges which was, I've never heard an ad on the radio from them and it talked about their angle was training medical professionals and talking about having not enough people to house an emergency room, take care of an emergency room and so forth. It was a very dramatic radio ad as you might imagine but their message was we simply all the cutting that has to be done that government will have to do over the next few years we have to preserve training of health professionals and medical research so they kept linking those two. So again, I think advocacy groups are starting to launch their campaigns and thank goodness they are. But it was just interesting, I'll be curious if other people hear that ad or we see similar ads from similar groups. Well, you could imagine that such budgetary scenarios cause grave concerns for NIH employees both because of our own job situations but also because the programs that we work so hard to support are all going to be threatened. Well, Senator Ben Cardin shown here who's the junior senator of Maryland held a town hall with NIH employees on August 31st and was actually preceded by a private meeting he had with the group of institute and center directors. I can tell you that in both venues he talked passionately about the state of the economy the complex situation with the current federal budget and his concerns that this might have to do with workers and on NIH. Now he's a very strong NIH supporter as you might imagine, NIH being based in his state and he promised a good fight to preserve and he would actually like to see improve our budget. But he also admitted to being involved in the strangest political situation he has faced in his long and distinguished career. In the end he expressed a cautiously optimistic message but he also stressed the need to be realistic about the likely difficult times we'll face over the next two to five years. Okay. That's the NIH. Let's now move into our field. So genomics updates. Ron Davis won the Gruber Genetics Prize which is awarded for the pioneering work in biotechnologies that advanced the for his work in advancing the fields of molecular genetics and genomics. Ron has been director of the Stanford Genome Technology Center since 1994 and will receive $500,000 for this for developing DNA mapping methods for studies of ways to sequence genomic variants in humans and other animals and for his contribution developing the first microarray technologies not to mention his work that his lab has done in sequencing yeast chromosomes, sequencing part of the E. coli genome and several other genomes. David Housler, a professor of biomolecular engineering at the University of California Santa Cruz has been awarded the 2011 Weldon Memorial Prize by the University of Oxford. Prize is awarded for contributions to the development of mathematical and statistical models to be applied to problems in biology. David is director of the California Institute of Quantitative Biosciences and he and his team's work has focused on using bioinformatics to understand the human genome for example by analyzing data from the cancer genome atlas by developing the cancer genomics browser and by founding the Genome 10K project. Remy Atasokin has been recognized by MIT's Technology Review Magazine by being among their 35 innovators under 35 honorees for 2011. He was honored for his work and the application of next generation sequencing to clinical diagnostics. Specifically he founded a company called Pathogenetica which aims to develop sequencing technologies to diagnose infectious disease. He is an alumnus of the Diversity Action Plan supported smart summer undergraduate research program at the Baylor College of Medicine Genome Sequencing Center. Now the TR35 list as it is called recognizes the world's top innovators under the age of 35 and includes those in a range of fields spanning from energy, medicine, computing, communications, nanotechnology and other emerging areas. I thought I would just briefly tell you that in August of this year I traveled to India on I guess what could be called a good will tour in genomics of sorts on behalf of NHGRI the initial and I thought I would just tell you a few things about this. The initial purpose of my trip was to be a keynote speaker at a Founders Day celebration commemorating the first anniversary of establishing the National Institute of Biomedical Genomics in India. This is a new institute just outside of Kolkata. I actually had some history with this institute being involved in some advisory input that they received about its potential creation back in 2008. Then opened its doors in 2010. This institute does represent a fairly significant development for genomics research in India which is why I decided to go and participate in their Founders Day. But as long as I was there I used the opportunity to tour several other genomics research facilities in India selecting the specific places based on some really good input that Aravinda Chakravarti provided about places that were rapidly accumulating genomics expertise. So I actually, it was a rapid fire trip was one of these things where I visited four research facilities in three cities over five days. I specifically went to two places in Bangalore Kolkata and one in Delhi. And in that short time I can tell you I met with a lot of investigators and many, many trainees and also some government officials. I could probably spend a long time describing my various findings and some of the things I still have questions about. And I'm happy to talk about that at the break. But to be brief I just would share with you some of my most notable observations were as follows. First of all it's impressive how India is making significant investment in research infrastructure especially in genomics building, lots of new laboratories quickly being put together. Second thing is it's very clear that Indian researchers are absolutely getting access to cutting edge genomic technologies. Every place I went they were unboxing a next gen sequencing instrument or two or three each of the places absolutely had access to that technology. I'd also tell you the research funding situation is quickly improving. It doesn't seem to be the rate limiting stuff in many ways that they really not like what you see here. They're not complaining about funding, they said they have the opportunities. Interestingly though, my fourth observation they're actually suffering from the same computational and bioinformatics bottleneck that we have in the U.S. despite the fact that many of their students are training in computer science. But the great great great majority of those who train in computer science go into the private sector because their salaries are ten-fold higher than what could be paid in the research settings in genomics. So I went there thinking I was going to encounter just tons of really good bioinformaticians and it seemed in a similar state that we were at for different reasons. So I thought it was just very interesting in any case I just wanted to share that with you. Okay, so for a little bit of lighter moment in the middle of my director's report I want to tell you about a new feature I'm going to add to the director's report I'm going to call Genomics in the news. These are supposed to be real, they are real examples but hopefully a little bit of fun. I just want to highlight some recent genomic news features and that I thought really caught my attention. And to start off this new feature I would point out we have sequencing analysis of the potato genome as recently featured on this awesomely wonderful cover of nature. I thought the potato based food objects to create a double helix was a work of genius and I just thought I hope you recognize that. Really have I seen French fries used in such an important way. More seriously, potato is the world's third most important crop. And analysis of the genome sequence data genome contains at least 39,000 protein coding genes far more than the human genome which I think in part explains the brilliance of Mr. and Mrs. Potato Head. I personally found this to be a spectacular genomic advance. Sorry, I had to do it. Preparing this report is really tedious so I got to throw in a few just to make me laugh while I'm preparing it. Notably interesting creatures that have had their genome sequence lately include the the Tasmadian devil the branching coral acropora digifera, I think is how you pronounce it and the Tamarwalabi. Now, why did I group these three together? There's actually great science behind each of these genomic studies but I put these three scientific stories in the news because they're simply fun being serious forays into the sequencing of creatures that have heavily been featured in cartoons over the years. Another major genomic story relates to the significant news coverage about the sequencing of the Marijuana Genome. Specifically, a new company called the Dysadyl Genomics announced in August that it had generated a draft genome sequence of the Marijuana plant at Cannabis Salvativa. Company scientists became convinced to pursue this research after seeing papers published in academic journals about the plant's tumor-trinking effects and rats and so they started a company around the discoveries with that genomic data. I've heard that if this company goes public they might offer reefer options instead of stock options but that might just be a rumor. Just testing you, seeing if you're paying attention. Okay. And now my favorite genomics news story from the past four months. CNN reported that a new Hampshire apartment complex is mandating that residents submit their dog's DNA via simple mouth swab if they want to have their dog in their apartment. They are then analyzing the DNA in any dog waste found on the premises and then using the proprietary quote, poop prints program I kid you not, the poop prints program to match DNA in the unclaimed dog waste to the DNA provided for each dog in the complex. Successful matches would indicate the guilty residents. You laugh but the program is currently assisting similar complexes in multiple states as well as increasing interest from as far away as Canada and Germany. I just, you know, we're very proud of our advancing genomic technologies program because with it we not only will save lives we will also keep the environment clean. But I would also note how I am staying away from any Elsie jokes about this although I could think of a few good ones especially related to incidental findings and also surprising paternity evidence but I'm just going to leave those to your imagination for now. My last genomics in the news item is timed perfectly to the individual who just walked in the door. It relates to the fact that baseball players are not the only ones getting high priced salaries due to free agency and the growing interest in genomics has caused exciting growth in the pursuit of superstar free agent genomicists. And it turns out that the biggest free agency signing since the last council meeting was council member Dave Valley who was lured to the Broad Institute for a lucrative contract and a really big office right next to Eric Landers' office. So actually just kidding, this is just a little bit of my humor this was actually the name placard that was put out for David at this genomic medicine meeting in Chicago and he arrived and saw it and he wanted to know if we were sending him a hint or something or maybe Hopkins was sending them a hint or something so that was a real sorry, okay so that was my genomics in the news. We will move on to more serious stuff now and talk about developments in the extramural program. Well the most active issues associated with our extramural program relate to the renewal of our large scale genome sequencing program. The program represents just a little over a third of our entire budget for our extramural program and as many of you know in renewing the program we issued four RFAs in the indicated areas shown in the slide. So Adam Felsenfeld is actually going to be giving a presentation about the history of our large scale genome sequencing program and provide additional details about these RFAs and then discussion about the review of these applications that in response to the RFAs will be discussed during the closed session of Council later today. In terms of recent accomplishments by our large scale genome sequencing program one highlight was in the area of comparative genomics. Using the draft genome sequence researchers at Baylor College of Medicine published a genome-wide SNP resource for Indian origin Rhesus monkeys one of the most widely studied non-human primate model in biomedical research and identified many potentially harmful non-synonymous coding SNPs. Another comparative genomics highlight was performed by Brode's Institute recent sequencing and analyzing the genome of the North American green anole, a little lizard, looks a lot like the Geico lizard I thought. Their study found that the whole genome of this lizard contains about 17,500 protein coding genes, 4,000 of which are also found in human, which explains by the Geico lizard talks during commercials that around 30% of the genome is comprised of mobile elements and contains 12 micro chromosomes. They also identified the lizard's sex chromosomes which appear to be XX and XY with the X chromosome being one of the lizard's micro chromosomes which was sort of interesting. In the area of medical sequencing our large scale genome sequencing program continues to be quite active and in fact there's some large and impressive studies reaching mature stages in terms of analysis. Specifically these include studies of diabetes and metabolic syndrome, autism lipid levels and tumor sequencing projects outside of TCGA and so you can see a lot of analysis a lot of these projects are really reaching mature stages. The cancer genome atlas program continues to make great strides towards its ambitious goals. Remember that with the economic stimulus investment two years ago TCGA was named an NIH signature project and it's an announced its intent to initiate 20 new tumor sequencing projects following the pilot effort on glioblastoma and ovarian cancer and also to accrue the characterized specimens from 3,000 cancer cases by September of this year. The list on the right shows the active 22 projects in TCGA right now. Accrual has actually closed for glioblastoma ovarian colorectal and renal cell renal clear cell carcinoma meaning the goal of 500 cases qualified for these projects has been achieved. This graph shows in blue the cumulative shipment of samples not including the pilot projects from January of 2010 to August 15 of this year. As of that date over 3,700 cases have been shipped to centers and the red line shows the generation availability of genome sequence files as a measure of data out of the project and even with the challenges of data management TCGA will achieve the goal for the September deadline I told you about earlier. And representing the type of reports expected from TCGA the research network published the findings from their ovarian carcinoma project earlier this year. The study included analyses of copy number gene expression promoter methylation on 489 high grade carcinomas plus exome sequence data of 316 of the specimens. The study represents the most extensive and comprehensive cancer genome study to date and it's the fifth most highly ranked article in molecular biology as assessed by the scientists but the good news is on top of that there's several upcoming manuscripts to watch for including those reporting the results of colorectal carcinoma, acute myeloid leukemia and breast carcinoma. One notable highlight an additional highlight for TCGA and also for NHGRI came in the June 13th issue of Time Magazine you can see that on the cover and within Time that issue of Time was an article on cracking cancer's code and it was a very well done article but the call out quote that they used in the article was by none other than Brandt Ozenberger at NHGRI who directs our cancer genome atlas component of the program where he says we expect ten years from now each cancer patient is going to want to get a genomic analysis of their cancer so that's great when NHGRI staff is recognized in places like Time Magazine. Congratulations Brad. The 1000 Genomes project continues to make great progress towards its goals Phase 1 sequence data and associated numbers include low coverage sequencing on almost 1100 samples or exome sequencing on over 1100 samples to date 39 million SNPs, 100,000 indels, 84,000 structural variants catalogued and integrated data sets going to be released next month. Beyond that of course is Phase 2 sequence data being generated this fall both low coverage and exome sequencing data being generated for over 1700 samples. The next 1000 Genomes project meeting will be held October 10th and 11th before the International Congress of Human Genetics in Montreal. In addition there's 1000 Genomes data tutorial will be held during the International Congress this sold out at last year's American Society of Human Genetics meeting with 500 participants and advertisement about this session has received almost 4,000 hits so far. So we expect probably a standing room only at that upcoming workshop. Before leaving discussion about our large scale genome sequencing program I thought I would mention that has reached a fairly serious set of strategic discussions including discussed extensively last week at an all day retreat of the institute directors. Bottom line there are some early discussions about the desire to develop a trans-NIH inventory of ongoing genome sequencing projects. Initially Francis Collins was interested in pursuing this for target validation to aid therapeutic development efforts but as more and more discussion around this topic has taken place there's a growing list of desirable aspects of compiling such information and developing such data sets and the associated cohorts. So Francis asked Terry Minolio to assemble a trans-NIH committee and do an initial analysis of ongoing and genome sequencing projects which he did in about a five week period that was presented last week and it really did reveal some interesting and very encouraging facts and figures. For example that across NIH there's studies funded and planned over the next few years to generate whole genome or mostly whole exome sequencing for about 75,000 individuals and with phenotype data available on some and varying levels of sample availability and other information that would become very relevant for the kinds of inventory and their possible uses. So there's really a significant momentum gathering about such an effort. There's going to be upcoming workshops there's also a private sector interest potentially in funding what would be required to pull all this together. Pharma has sort of indicated the desire to maybe share the cost associated with this and obviously a growing list of possible projects one might be able to pursue if you had such data sets available in one place. So last week at this retreat of institute directors not surprisingly NHGRI was now asked to be the lead institute on such an effort and so I would fully expect that you will be hearing more about this at future council meetings as things develop. So I just wanted to put that out there and you can certainly ask her questions being very involved in this over the last month. Adam Felzenfeld served as the NHGRI representative he also knows quite a bit about this but I'm reasonably convinced that something like this is going to happen and I'm sure we will be bringing this to council for additional information updates. Yes. Eric is that draft inventory publicly available? Well which things are where? I don't think yet but I don't think you'd want to be... I mean this was done rapid fire I would say it's worth now doing this in a much more rigorous way. The information, you could ask Terry when she gets here about what information is shareable but I'm not sure you'd trip up over a lot of this I suspect at first. Maybe interesting. So I just a little clarification is the effort to to get a better inventory or is the NHGRI effort to actually get the data all together in a way that it can be distributed in years? The first effort was to figure out what's out there and is it worth investing to try to bring it in under one data warehouse? Based on the preliminary inventory it seems that there's a lot out there and it's probably worth bringing in probably some pilot studies to see how well that works but again this is being spearheaded by private sector interests to potentially fund the gathering of this because it would be expensive to bring it in under one roof. So stay tuned. So for NHGRI's program it aims to reduce the cost and increase the rate and quality of DNA sequencing nine awards were made for applications that were discussed at this past May's council meeting the commitment over the life of these grants is just a little over 14 million dollars and these projects will explore a diverse a set of applications including those listed here and you can just read the different areas and we discussed them at the last council meeting. So these are some very exciting technologies that we are very much looking forward to seeing how they develop with these new grants but meanwhile new applications for DNA sequencing technology development are due later in the middle part of next month so we hope to have a continued infusion of good ideas for this program. Relevant to technology development the NIH has reissued a program announcement for small business SBIR grant mechanisms specifically R43 and R44 in the area of developing tools for biomedical and behavioral research. This is an NIH wide program through which NHGRI could fund relevant applications the program announcement encourages the translation of technologies for biomedical or behavioral research from academic and other small non-small business research sectors to the marketplace it's important for NHGRI particularly for the translation of genomic technologies especially genome sequencing technologies and applications are due in early November Moving on to encode and mod encode NHGRI is in the early planning stages for a mod encode symposium that will be held on the NIH campus on June 20th and 21st of 2012. The goals of symposium are to broaden community understanding of model organisms and to showcase the contributions of the mod encode consortium. We've now worked it out so the meeting will tie into the upcoming model organisms to human biology genetic society of America meeting which is also scheduled for June 2012 in the Washington D.C. areas. These meetings essentially will be back to back. In addition to that there's integrated analysis papers actively being developed both in the encode and mod encode consortium are currently in the writing phases for integrated analysis papers. Encodes going to coordinate their publications to feature a main integrative paper, multiple high-profile companion papers and then many companion papers. And mod encode is working to integrate worm and fly data and if possible bring in the human encode data. The encode technology development FOA was released after May Council and the applications were received in early August. Applications will receive peer review in the fall and then council review during the February meeting. For our Centers of Excellence in Genomic Science program a 1-2 award was made this year. Aviva Gev and her colleagues at Broad Institute Mass General Hospital in Harvard will establish a center for cell circuits and will develop reagents, technologies, algorithms, protocols and strategies for reconstructing molecular circuits. We'll test these innovations by applying them to two circuits in the million cells. One transcription response to pathogens and dendritic cells as an example of acute response to environment and two control of chromatin organization and gene expression and mouse embryonic stem cells as an example of circuits that underlies stable cell states. And dissemination of tools is an explicit goal of this center. With the addition of this new SEGs we currently have eight active awards in the program and two centers that are phasing out of the program after their ten years of support. Updates on our mouse knockout projects comp and comp2 include the following. Comp the knockout mouse project winds down at the end of September as of August 1 8700 knockouts have been produced and the goal was 8500. Recall that comp2 is an effort to phenotype knockout strains produced by comp. For comp2 awards we made this fiscal year. Overall funding for the program is 111 million dollars over five years and the goal is to produce and phenotype 2500 strains. I also tell you that there will be a major meeting this month that will reflect the finale of comp and the kickoff of comp2 and the launching of the international mouse phenotyping consortium, otherwise known as IMPC. For our LC research program there are three new program announcements that were released in July. The R01 component is designed for medium to large multidisciplinary studies. The R03 component is targeted to small self-contained analytical or conceptual projects that can be done in two years for up to $50,000 per year. The R21 component is aimed at cutting-edge exploratory development grants that are taking on new or rapidly evolving ethical issues or the implications of emerging or anticipated scientific and technical developments. The R21 component can be requested up to two years in a total of $275,000 in direct costs. The announcements focus on the issues raised in the new strategic plans genomic and society section such as those that are listed on the slide. I would point out that a number of other NIH institutes are participating in this program announcement including NCI, NIA, NICHD, NIDCD, NIEHS, and NINDS. I hope all of you know what all those abbreviations stand for. If not, I could tell you. Okay. In July, NHGRI held a meeting to discuss data sharing as it relates to research ethics and policy. The meeting was organized by the consent and community consultation work group and its goal was to explore how ELSI research in partnership with genomic research studies like eMERGE can inform the development and implementation of research policy. The meeting focused on the impact of data sharing policies on researchers, research participants, and community partners. And the meeting extensively explored how data on these issues can be used to inform the development of research policy. In addition to researchers, bioinformatics experts, and community advisors, meeting participants included NIH, OHRP, CDC, Veterans Administration, FDA, and the Institute of Medicine program officials, group health, pharmaceutical and biobank representatives, and members of professional societies and patient advocacy groups. And a journal article summarizing the workshop discussion is being planned. Speaking of meetings, let me just let you know. In October, there will be a meeting of our CERS program. Then at this year's International Congress for Human Genetics meeting in Montreal will be a session organized by our ELSI program entitled Emerging Ethical Issues in Large-Scale International Genomics Research Collaborations. Later in October will be our annual meeting of our SEGs and Diversity Action Plan programs to be held in Boston. And finally, in December, a workshop addressing approaches characterizing genetic variants for clinical use will be held in the D.C. area. The goal of this workshop is to identify the resources and pipelines needed to decide on the clinical relevance of genetic variants and how best to disseminate this information to support clinical use. And I mentioned this earlier because Mark Williams, along with Rex Chisholm from Council, are co-chairing the planning committee for this workshop. Those activities are an extramural program now moving on to common fund programs that NHGRI is responsible for or in part responsible for. Let me tell you that in June 1 of this year, the NIH Common Funds Molecular Libraries program began the fourth year of its production phase, the pilot phase plus the production phase to date total six years, so it's actually beginning the seventh year of the program overall. Meanwhile, it met its annual quantitative goals in year three. Those goals are 20 or more new projects per center, 15 or more active chemistry projects per center, and 10 to 12 approved projects by peer reviewed per center per year. Overall, the molecular libraries network has accomplished an impressive set of achievements. They've accepted 490 high throughput assays, they've completed over 180 chemistry projects, and they've produced 229 small molecule probes. While there is a future focus on quantitative milestones, these are obviously more difficult to set, and nonetheless these include aiming to generate higher quality probes and better characterized probes. A network of centers working together are now working to identify appropriate benchmarks for these qualitative milestones. In terms of areas being served by the molecular libraries effort, shown here is a distribution of health areas for which projects have been or are being pursued. I think as you quickly scan across that pie chart, you'll see the diverse and balanced portfolio of projects assigned in the molecular libraries program. It also shows a good distribution of biological targets that would be of interest to most NIH institutes and centers. Here is a very nice highlight of the molecular libraries program. A lead compound was discovered in the molecular library small molecule repository by the Scripps screening center in the first year of the molecular libraries program. This was approved as probe ML007 in February of 2007. In only five years, Scripps was able to complete lead optimization and pre-clinical testing of analogs of ML007 and submit an IND in January 2011 for the treatment of multiple sclerosis. The compound remains in phase one testing, but the results have not yet been disclosed. Of note, this is the first probe from the molecular libraries program to have an IND filing. And another recent highlight from the MLP molecular libraries program was a little closer to home, was accomplished by the NCTT National NIH Center for Translational Therapeutics which sits within NHGRI as I told you earlier led by Chris Austin and was featured on the August 5th issue cover of Science. The project reflects a major collaboration with investigators here at NHGRI at NIAID at Columbia University. They used a combination of quantitative high-throughput screening and genome-wide association analyses to identify 32 highly active antimalarial compounds and genetic loci associated with differential responses to those drugs. These findings give both new leads for antimalarial treatments and insights into mechanisms of resistance to current drugs. The reason this paper is particularly notable sort of is a tour de force of chemical genomics, that is, it's a combination of chemistry and genomics to discover fundamentally new insights about biology and disease. Moving on to the human microbiome project, once again, significant progress can be reported to date. There's 108 publications in PubMed that cite HMP support. There are two major papers from the HMP Consortium nearing completion an HMP resource paper and an HMP analysis paper on the 300-subject healthy adult microbiome core hole study. There's anticipated submission of these papers this fall. The pilot phase of the genotype tissue expression or GTACS project is now out of the gates and while initially slow, recruitment is now well underway with two dozen postmortem donors in role. Laboratory analysis is ongoing and we just had the first in-person meeting of the external scientific panel this past June. We'll say about GTACS because Jeff will make a presentation about this Common Fund project later in the open session. The next Common Fund project is Lynx, a library of integrated network-based cellular signatures in October of this late in October. The Lynx program will hold a fall consortium medium in the DC area that will involve members of the production centers as well as newly awarded collaborative supplement technology development and computational tools. These were conducted this summer for U01 applicants in computational tool and advanced technology development. We expect to fund eight awards from the applicant pool based on final feedback by NHLBI and NCI September Councils. The Lynx production centers at Harvard Medical School and the Broad Institute have created public websites to inform the community about release data through its data browser also to discuss current experimental components of the program and to the Lynx program. For the relatively new NIH Common Fund protein capture reagents program applications for the production and technology development components will be discussed later in the closed session of Council and meanwhile there will be a consortium meeting with all newly funded grantees and current members of the program in winter of 2011 somewhere here in the DC area. This is an exciting period for science in Africa as featured and discussed on the cover of this issue of nature and there are many things that are being watched and being pursued in Africa but the NIH Common Fund's contribution to this is H3Africa the Human Heredity in Health in Africa project which is initiative to support population based genomic studies to study diseases relevant to African people but these studies are performed by African scientists in Africa. This is a joint effort with the welcome trust and as you will likely recall H3Africa is the lead institute for NIH H3Africa and much has happened of late in this project and so Jane Peterson will be given an update about H3Africa later in the open session. Now finally with respect to the Common Fund by design we're called the Common Fund projects sunset or at least scale back over time allowing new Common Fund projects to be launched so there's not a regular process for identifying and developing possible new programs that will be supported by the Common Fund. Well in May of this year there was an innovation brainstorm meeting and for this meeting institute directors nominated very junior investigators to participate in this gathering where new ideas were kicked around and discussions were held. Attendees that are familiar to NHGRI although not all these people were nominated by NHGRI other institutes nominated some of them including Gonzalo Abacases, Brad Bernstein, Manolis Kellis and Brad Malin among the topics rigorously discussed in this meeting was the possibility of a new microbiome oriented program. In addition to somewhat broad ideas that emanated from this brainstorming meeting each institute and center was invited to submit up to two new Common Fund ideas for further consideration NHGRI's two proposals were in the area of disruptive proteomic technologies somewhat modeled after our DNA sequence technology development program and our second one was molecular phenotype for genome function disease very much oriented towards a post GWAS effort at understanding the molecular basis of disease phenotypes and we're now in a comment period at least until I guess it's till two more days. So if you haven't already and you're interested in looking at not only our proposals but all the proposals they came in from other institutes now is the time to get your voice heard there's an open comment period online so I'd encourage the next couple of days look at it and weigh in if you are interested. So that's our involvement with the Common Fund. Let me briefly now move on and tell you about developments in the Office of the Director. This is going to be a relatively short section because normally I would cover areas related to the Office of Policy Communications and Education but this council meeting Laura Rodriguez is going to follow me and describe in greater detail activities of that office which she directs. So I'll only talk about activities of the Office of Population Genomics in this particular case. So we will start off with a reminder the Office of Population Genomics oversees the Electronic Medical Records and Genomics Network or known as Emerge Network. This project has wrapped up its first phase which has included efforts of five investigative sites in addition to two genotyping centers and an administrative coordinating center within the Vanderbilt site. The network entered its phase two awards. Five to phase one sites but also two to do to new integrative sites and one award to a coordinating center at Vanderbilt. The goals of Emerge 2 are to demonstrate that patients genetic information linked to disease or clinical manifestations in the electronic medical records can be used to improve their care. Because Emerge 2 has no pediatric sites an RFA to solicit pediatric sites was released in July with applications due tomorrow. The Office of Population Genomics continues its excellent curation of the GWAS Catalog that continues to be exponential growth in the number of publications reporting GWAS findings which means our GWAS Catalog continues to grow at a significant rate. The latest complete summary goes through the end of the first quarter of this year and reflects 862 publications with 1,319 associations at P less than or equal to 5 times 10 to the minus 8 for 221 different traits. Remarkably besides this summary as of then our Catalog actually has now surpassed the 1,000th publication mark and that occurred on September 6th of this year. The last update from the Office of Population Genomics relates to the Phoenix project which published a paper describing the design of the Phoenix toolkit in the August issue of the American Journal of Epidemiology and I would also tell you that Phoenix also published a paper in the May issue of the American Journal of Preventative Medicine on adoption of standard measures in biomedical research. Now Phoenix has now teamed up with NIDA, the National Institute of Drug Abuse, for a one-year project to expand substance use measures in the toolkit for which NIDA is providing $730,000. This will involve convening three working groups of substance abuse and addiction experts who will be tasked with identifying measures that will expand the scope of the toolkit to include additional substance use and addiction measures to promote data harmonization within the NIDA and also the NIAAA grantee community. The Phoenix administrative supplement program had their kickoff meeting earlier this month and investigators are adding a variety of Phoenix measures to existing studies. Finally, the supplement program will also help us evaluate the overall usefulness of the Phoenix toolkit. We expect this work to be completed by fall of next year. Moving to the final area I wanted to say a few things about our intramural program and actually the first one I think is particularly relevant I want to remind you that in general council doesn't get too heavily involved in our intramural program. We have a separate Board of Scientific Counselors, actually with Sean Eddy currently serves on that oversees in greater detail our intramural program but there is one development that I want to make council particularly aware of because it sort of goes at a level even higher than our standing Board of Scientific Counselors. Really this is the most significant development that's taking place in our intramural program and it relates to something called the blue ribbon panel review. Now blue ribbon panel reviews of intramural programs of NIH institutes is something that was started actually by Harold Varmas when he was director of the NIH and the idea was to augment the detailed reviews that take place of individual investigators every four years with sort of a higher altitude holistic review of an intramural program much less frequently and in fact by policy Harold put into place that such a high level external review should be conducted of every intramural program every 10 years once a decade and so for a variety of reasons I actually decided to conduct a blue ribbon panel review of our intramural program there are actually several reasons for that that I'm happy to share first of all turns out that our last blue ribbon panel review of our intramural program took place in 2001 so we would do it was 10 years and we should be doing this anyway but it also was recognition that a lot of new leadership on board we have a new scientific director of our intramural program I knew deputy scientific director and I'm relatively new to this job so it's a whole new leadership team at the institute seemed like an appropriate time to get some good external advice about the program I'd also point out the new strategic plan for the institute is obviously out and I think the intramural program is very interested to hear lies council on how they are aligning to that strategic plan how they could be enhancing certain areas how they can play to their strengths and also there's probably too many opportunities for intramural researchers and too many things to do and they have to make prior decisions getting some input at a higher level at a programmatic level I thought would be very helpful and then needless to say just it's very hard to manage any science inside of NIH outside of NIH during fiscally challenging times and intramural program is going to have to do that like everybody else and it was very clear that getting some advice on making tough choices in the face of budgetary cuts getting that advice now might prove to be very helpful to Dan Caster in particular in his first year now as scientific director so I put into place put into motion conducting such a review first thing I will tell you is that the review is handled not by the scientific director fact it's handled a level up it's handled by me in partnership with the NIH director at least that's how it's supposed to be in this particular case the NIH director's research program is in our intramural program so he's been pushed aside so Francis will have nothing to do with the review he's recused himself and instead Michael Goddusman who is the director deputy director of NIH associate director for intramural research he leads the office of intramural research at NIH and really oversees all the intramural programs he has stepped in and so he and I will be jointly overseeing this review and so I have now recruited this panel names are probably familiar to every one of you it was required to have a by policy a representative from both counsel and by our standing board to provide that kind of institute and intramural specific input Rick Myers has agreed to be the council representative and Bruce Korf has agreed to be the board of scientific counselors representative and as you can see otherwise we just sort of got a superstar studded cast of individuals who are willing to put in their time this is not a one shot one kind of meeting review it's about a nine month process it will involve a couple of face to faces and probably a couple conference calls it's pretty it's and it's really a very cerebral strategic back and forth kind of a process we hope I would it's sort of schedule to take place between now and at the beginning of next summer to provide advice for the beginning of the following fiscal year I will absolutely be we will be bringing the report and a presentation about this review to counsel because I think it's high enough level that counsel should be aware of this I would expect that'll probably happen a year from now because I don't think I'll be wrapped up by May so my prediction is a year from now we'll be updating you about this blue ribbon panel review getting on to the science of the intramural program let me just tell you a few recent research highlights from our intramural program one of those noble ones was was the discovery of the gene mutated and proteas syndrome there's a rare disorder that causes tissue and bone to grow out of proportion of the body there's a 15 year search led by an NHGRI research team by Les Beeseker and finally using next-gen sequencing discovered that mutations in AKT-1 are what are responsible for proteas syndrome a result they reported in this paper in the New England Journal of Medicine and interesting molecular insights from these findings may help establish the cause of the so-called elephant man severe disfigurement other recent highlights to quickly run through from our intramural program since last council meeting Chuck Venditti and colleagues reported a study where whole exome sequencing led to finding the gene for combined malonic and methamalonic aciduria increasing the likelihood of diagnosing this rare metabolic disorder NHGRI researchers published a study reporting that mutations in the NVEA L2 gene caused the bleeding disorder known as gray platelet syndrome in two studies led by Ken Kow working with Francis Collins provide new insights about Hutchinson-Gilford progeria syndrome when reported that cells from progeria patients responded to treatment with rapamycin which flushes accumulation of the toxic protein progerin from the cell and in a separate study these researchers showed that progerin is activated in normally aging cells as telomeres get degraded and a collaboration to generate a gene expression map of the mouse cerebral cortex between researchers involved researchers in we have music Martily's group at NHGRI and the Ponting group at Oxford University led by this Grant Belgard who is shown here as a joint graduate student between those two labs and that was also recently published I guess is there somebody on the phone who is on hold it must be saying about when the music starts it probably means I need to wrap up my director's report and the timing is perfect so what can I say we are at the end before I conclude I should once again help Chris thank her profoundly for helping me get this 85 slide PowerPoint presentation together but also thanks to Larry Thompson, Judy White and the web team for getting all this electronic resource and finally thanks to most of the staff sitting behind you and some that aren't even in the room because Chris goes out and coordinates all these activities there's probably about 40 or 50 people that put slides together for this presentation each time so we thank all of you this is a real group effort so I will stop there and answer any questions you may have at this time about anything I've covered Jeff when you were discussing NCATS you did mention the Cures Acceleration Network and maybe could you just update us as to whether that concepts is still on the table and can contribute to NCATS oh yes wow I won't know this in as much detail anybody in the back of the room or on the side of the room who know these details better than me please step to a microphone so the Cures Acceleration Network will happen it's been authorized but not appropriated so they actually have to put money in it and that's actually very important because that will trigger not only money it will actually trigger flexibilities with money that NIH normally doesn't have it's DARPA like flexibilities it's very important so that requires real legislation to kick that in whether that happens as part of the anomaly with the continuing resolution I don't know I actually just honestly don't know that I mean the long run that's going to likely happen it's just a matter of whether that happens with the real budget or whether that happens through the anomaly I actually don't know and I don't know if anybody else knows here but what I do know is at a minimum what they want to have happen within this anomaly is just to create the organizational creation of NCATS because even if that happens it allows the pieces to be moved around such as the piece out of NACRI to be moved under the roof of NCATS and allows the big piece from NCRR the CTSA program to move in and various other things so I think more than anything they just need that minimum permission for the reorganization and that can be just simply my understanding through an anomaly don't know about the, but I mean again care acceleration after absolutely still on the horizon it's a matter of what part of this legislative journey and nobody's jumping up and down which either means I got it right or nobody knows other questions?