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On March 17, Microsoft Research Connections and the São Paulo Research Foundation (better known by its Portuguese acronym: FAPESP) held a workshop to mark the ongoing collaborative efforts of the Microsoft Research-FAPESP Institute. The theme of the workshop—revisiting the past and planning for the future—provided the scientific community with a historical perspective on the Institute's completed projects, its ongoing initiatives, and the prospects for future investments.
Harold Javid, Director of Microsoft Research Connections, Carlos Henrique de Brito Cruz, Scientific Director of FAPESP and Michel Levy, President of Microsoft Brazil during the meeting MSR-FAPESP Institute Workshop: revisiting the past and planning the future.
The presentation of newly funded research projects broke with tradition this year: previously restricted to researchers and teams who are directly involved with the selected projects, the event was opened to all professionals and researchers interested in learning more about the opportunities created by the program. By so doing, the Institute reached out to researchers and scientists from other areas of knowledge, while simultaneously stressing the role of information technology in accelerating scientific research on priority themes.
The event was attended by Carlos Henrique de Brito Cruz, scientific director of FAPESP, and Michel Levy, president of Microsoft Brazil. Leonardo de Moura, a senior researcher at Microsoft Research in the United States who specializes in theorems and the optimization and verification of software, presented the first lecture, "Symbolic Reasoning @ Microsoft: Tackling Impossible Tasks." Harold Javid, the director of Microsoft Research Connections (a division of Microsoft Research) explored the theme of e-science, addressing such fertile areas for collaboration as medical imaging research, a new approach to creating digital narratives, and compelling possibilities for sharing "big time" views of history.
Announced at the workshop were the four projects that were selected in the latest call for proposals. The researchers who were responsible for the approved proposals then made brief presentations of their studies.
All of these endeavors align perfectly with the mission of the Microsoft Research-FAPESP Institute for IT Research, which is to support bold, innovative projects that apply technology to enable or accelerate research that will help humanity.
—Juliana Salles, Senior Program Manager, Microsoft Research Connections
There is a significant dearth of women working in—or even entering—the computer science field. According to the National Center for Women & Information Technology (NCWIT), only 18 percent of computer science degrees in 2008 were awarded to women. That was a dramatic drop from 37 percent in 1985. With those totals, it's not surprising that only 16 percent of Fortune 500 technology companies have female executives. Of greater concern is the small number of women who are applying for technology jobs, even during the economic downturn when jobs are scarce. NCWIT is working to reverse that trend.
Winners at the event held at the Microsoft New England Research & Development Center in Cambridge, MA
We are proud to be the primary financial supporter of the NCWIT Award for Aspirations in Computing, which honors young women at the high-school level for their computer-related achievements and interests. NCWIT offers both national and local "affiliate" competitions to generate support and visibility for women's participation in communities nationwide.
National Award winners receive a US$500 cash prize; a laptop computer provided by Bank of America; a trip to attend the Bank of America Technology Showcase and Awards Ceremony in Charlotte, North Carolina; and an engraved award for both the student and the student's school. Affiliate Award winners receive an engraved award for their home and school, plus additional prizes from local sponsors.
I'm pleased to announce that the academic community stepped up this year to offer scholarships to this year's NCWIT winners as well. There will be 19 Affiliate Award programs serving 20 states and U.S. territories in the 2010/2011 round. Schools expected to connect with our winners include:
The NCWIT Award for Aspirations in Computing is a promising avenue for reaching out to and encouraging young women with a budding interest in computer science. By nurturing this interest early, we are increasing the likelihood that these young women will pursue computer science degrees and one day join us as the next generation of world-class computer scientists.
—Jane Prey, Senior Research Program Manager, Microsoft Research Connections division of Microsoft Research
Researchers believe that pathogens are evolving to evade detection from the human immune system. I recently co-published a paper that discussed research into the ongoing evolutionary struggle between the immune system and pathogens. In this study, we sought to identify possible commonalities in HLA (human leukocyte antigen) binding preferences that would reveal patterns of optimization of this component of the immune system in response to the variation in pathogens.
I worked with post-doctoral student Tomer Hertz (now with Fred Hutchinson Cancer Research Lab) and a distinguished group of colleagues from the Institute for Immunology and Infectious Diseases, Royal Perth Hospital, and Murdoch University (Western Australia); the School of Anatomy and Human Biology, Centre for Forensic Science, University of Western Australia (Western Australia); and Fundacion Ciencia para la Vida (Chile).
Our paper, "Mapping the Landscape of Host-Pathogen Coevolution: HLA Class I Binding and Its Relationship with Evolutionary Conservation in Human and Viral Proteins," appeared in the American Society for Microbiology's Journal of Virology in February 2011. I'd like to share some highlights from the study with you.
Identifying Possible Commonalities in HLA Binding Preference
The majority of the cells in our bodies express something called HLA molecules, whose role is to sample cellular proteins and present them on the cellular surface for external surveillance by the specialized cells of our immune systems. This action forces all cells to reveal imprints of their inner workings.
When something out of the ordinary is detected—for example, the presence of an unusual mutation or a gene expression—the type and quality of the presented samples can spur the immune system's specialized killer cells into action. By sending kill signals to "odd" cells, the immune system can stop diseases such as cancer or viral infections. (Viruses bring their own genetic material to the cell and use the cellular resources to propagate.)
However, this scrutiny of the immune system creates evolutionary pressure on viruses, which often mutate to evade detection. Since the system of HLA molecules is highly selective in its sampling of protein segments, the mutational patterns in viruses are not entirely random: mutations tend to occur within the segments that HLA molecules are most likely to present.
On the other hand, over many generations, the distribution of thousands of HLA variants present in human populations may change. Additionally, in different geographic regions, we find significant variation in frequencies of different HLA molecules. This sets up an evolutionary game between the viruses on the one side and our immune systems on the other.
In order to analyze the results of the evolutionary processes that are driven by the interaction of HLA molecules with a wide diversity of viral intruders, we quantified the HLA binding preferences by using a novel measure called "targeting efficiency."
Targeting efficiency entails capturing the correlation between HLA-peptide binding affinities with the genetic conservation in the targeted proteomic regions. If HLA molecules possessed such targeting efficiency, this would (presumably) prove beneficial to humans. In theory, HLA molecules would draw attention to protein segments that are shared across related viral species as functionally important and thus immutable sections of their proteins. Individual invading viruses would find it more difficult to evade surveillance by mutating, because mutation within these segments would ruin the protein function. Targeting efficiency could even allow the immune system to generalize across related viral species.
Our analysis of targeting efficiencies for 95 HLA Class I alleles over thousands of human proteins and 52 human viruses indicate that HLA molecules do indeed prefer to target conserved regions in these proteomes! However, the arboviral Flaviviridae (for example, Dengue virus) proved a notable exception in which non-conserved regions were the preferred target of most alleles.
HLA molecules are encoded in three separate parts of the human genome: A, B, and C. During our study, we discovered that the oldest versions of our HLA molecules—namely the HLA-A alleles and several HLA-B alleles that had maintained a close sequence identity with chimpanzee homologues—were targeting conserved human proteins and DNA viruses (for example, Herpesviridae and Adenoviridae) most efficiently.
By contrast, the HLA-B alleles were targeting RNA viruses efficiently. This is reminiscent of predator-prey patterns that have been identified in evolutionary theory. For example, we know the following factors to be true:
Based on this information, we can extrapolate that evolution is going to drive their binding properties in different directions, thus splitting their targets, as in the established Lotka-Volterra (predator-prey) model of different types of foxes and rabbits inhabiting the same forest. In addition, we identified various patterns of host/pathogen specialization that are consistent with co-evolutionary selection and were also functionally relevant in specific cases. For example, preferential HLA targeting of conserved proteomic regions is associated with improved outcomes in HIV infections as well as protection against Dengue Hemorrhagic Fever.
I have just scratched the surface of the study in this blog. For complete study details, including a complete presentation of our methodology and findings, please follow the links below.
—Nebojsa Jojic, Principal Researcher, Microsoft Research eScience Group