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HIV infection may not be the death sentence it once was, but it remains an undeniably serious condition that requires aggressive, life-long treatment and entails the ever-present threat of severe immunological impairment. Consequently, medical researchers continue to investigate the mechanisms by which HIV infection evades detection by the body’s normal immune responses. In the August 3, 2011, issue of Nature, investigators from the Ragon Institute of MGH, MIT, and Harvard; Imperial College London; the National Cancer Institute; and Microsoft Research have shed light on the interactions of HIV and the immune system’s natural killer (NK) cells. Our paper is the first to show that NK cells play a direct role in fighting HIV. This knowledge opens a new path of research into ways to beat the virus.
Scientists have long known that NK cells play an important role in the control of viral infections, mounting short-lived but highly toxic assaults on infected cells. NK cells bind to virus-infected cells, releasing proteins that destroy the target cells. To regulate this cytotoxic potential, the membranes of NK cells are studded with activating receptors, which unleash the cell-killing response, and inhibitory receptors, which keep it in check.
It’s logical to expect that NK cells would play a role in the control of HIV infections, and, in fact, various in-vitro and epidemiological studies suggest that NK cells do just that. For example, research has shown that the population of NK cells increases during the earliest phase of HIV infection and that NK cells can suppress HIV replication in cultured tissues. Moreover, epidemiological evidence indicates that infected individuals who have particular versions of the genes that code for a class of NK cell receptors called KIRs (killer immunoglobulin-like receptors) are better able to control HIV levels. However, it remained unknown whether NK cells directly mediate anti-HIV immune pressure inside the human body.
We wanted to test the hypothesis that mutations in the HIV proteins that are recognized by KIRs could allow the virus to escape NK cell activity. Proving this hypothesis would support a role for NK cells in HIV control. After analyzing the sequences of both HIV proteins and the genes encoding KIR molecules from 91 infected individuals, we found that particular variants in viral proteins were associated with specific KIR genes. This finding suggested that the virus mutates in response to NK cell activity. In particular, we found individuals whose NK cells included an inhibitory receptor called KIR2DL2 were more likely to have variant forms of HIV that enhance viral interaction with that receptor. Those results suggest that the HIV mutates into a form that interacts with the inhibitory receptor, thereby preventing NK cells from attacking HIV-infected cells.
Microsoft Research was intensely involved in this study. The first tell-tale signs that NK cells were affecting HIV were found by using a sophisticated software tool that was developed at Microsoft Research. The tool used almost a CPU-year of computation to sift through millions of possible clues as to how our immune system interacts with this deadly virus.
Our study provides hope that a greater appreciation of the NK-cell-mediated immune responses to HIV can lead to therapies that interrupt the virus’s evasive processes, thereby giving physicians another weapon in their long-running battle with HIV and AIDS.
—David Heckerman, Distinguished Scientist, Microsoft Research
Collaboration can be a great catalyst for new ideas. Whether working with colleagues from down the hall or a team from another continent, we have found that working together strengthens our ideas. A prime example is the Barcelona Supercomputing Centre – Microsoft Research Centre in Barcelona, Spain. Microsoft Research Cambridge began collaborating with the Barcelona Supercomputing Center (BSC) in 2006. We formalized the relationship with the establishment of the BSC – Microsoft Research Centre in January 2008. The Centre focuses on the design and interaction of future microprocessors and software for the mobile and desktop market segments.
The BSC – Microsoft Research Centre is home to a talented group of students who are working towards their PhDs and who bring their creativity and enthusiasm to tackle tomorrow’s problems. “I am very happy that the Centre is a model of open research,” said Centre director Mateo Valero. “We share our findings with the community and all of our software and applications are available for download at our website.”
The program has an extremely young team with more than 15 PhD candidates, Valero explained. Leading the student group was Ferad Zyulkyarov, who is at the forefront of Transactional Memory (TM) research. Working under the supervision of Valero, and his colleagues Osman Unsal and Adrián Cristal, Zyulkyarov investigated how this new approach to multi-core programming could make software development much easier for future computer architectures.
Ferad Zyulkyarov defends his thesis in Barcelona
A Different Point of View
Previous TM research had focused on evaluating and improving TM implementations. Zyulkyarov took a unique approach to the problem, looking at it from the programmer’s point of view. As part of his thesis, Zyulkyarov developed one of the first real-world TM applications: a rewrite of the Quake Game Server that replaced traditional memory locks with TM atomic blocks. This makes life much easier for the programmer, potentially transforming multi-core software development for the future.
Zyulkyarov encountered some obstacles during his project. For example, he had to develop a better debugger and profiling support, neither of which existed before he created them. When he reviewed the performance of the core server code, Zyulkyarov could see the potential for TM. There is still some optimization work to be done, but the potential is there.
During the project, Zyulkyarov collaborated closely with Tim Harris, senior researcher, Systems and Networking Group, Microsoft Research Cambridge. Harris is proud of the work Zyulkyarov accomplished during their time together. “It’s great to see Ferad’s work come to fruition,” Harris said. “He’s made substantial contributions to the development of programming tools for using TM, and I hope that we’ll now be able to apply these ideas to other parts of the multi-core challenge.”
The First of Many PhDs from Barcelona
The first of the 15 students to receive his PhD, and now at Intel, Zyulkyarov is just one example of the young talent being fostered through the BSC – Microsoft Research Centre, driving the industry to tackle some of its most challenging problems. “In the five years since we have started, the Centre has matured quite a lot, and this is the first fruit of the collaboration with BSC and Microsoft Research,” Valero said, adding he is especially grateful to Harris for serving as Ferad’s mentor. “I know that more [success stories] will follow soon,” he added.
I am very glad—thinking back to my first visit to BSC five years ago—in seeing how far we came. This is the result of all the energy and enthusiasm we have all put together in the enterprise. This is only the first of a successful series of PhD awards, which we will see taking place in the next few years.
—Fabrizio Gagliardi, Director, Microsoft Research Connections EMEA (Europe, the Middle East, and Africa)
As the saying goes, “Seeing is believing.” But with computers, that’s only half the story. Cameras are becoming an ever-present part of our world. They are built into cell phones and laptops, and dot the landscape in storefronts and on street corners. Their pervasive images present us with a wealth of information. So how do we extract information from these images and use it?
One hundred excited students from across Russia and the Commonwealth of Independent States (CIS) converged at Moscow State University for the 3rd Annual Microsoft Research Summer School.
That question set the scene for 100 excited students from across Russia and the Commonwealth of Independent States (CIS), a quarter of whom were women, who converged on Moscow State University (MSU) for the third annual Microsoft Research Summer School. This year’s session focused on the intricacies of computer vision, with activities led by Microsoft Research experts and leading European academics.
The summer session began with a special welcome from Nikolay Pryanishnikov, president of Microsoft Russia. “Supporting young talent is traditionally one of our key strategic priorities,” Pryanishnikov told the students. “We are confident that, with the help of events like this Microsoft Research Summer School, our young specialists will be able to realize their ideas, reach new peaks, and increase the innovation potential of the Russian economy.”
The students were busy throughout the week; each day was packed with intensive academic talks, demonstrations, and hands-on laboratory sessions that were designed to educate attendees about fundamental and state-of-the-art techniques in computer vision. Andrew Fitzgibbon, a principal researcher at Microsoft Research Cambridge, gave a detailed description of how decades of computer vision research, along with ground-breaking ideas from Microsoft Research, came together to make Kinect technology a reality. The summer session also featured industry talks: Aram Pakhchanian of ABBYY, a Moscow-based company that specializes in optical character recognition, and Michael Nikonov of iPi Soft, a company that specializes in motion capture technology, talked about how to create a startup company in computer vision.
Andrew Blake, managing director of Microsoft Research Cambridge, was delighted to lecture and talk to the enthusiastic students. “It was clearly a splendidly vibrant event, with tremendous enthusiasm from the students,” he said. “This really is a landmark event for Microsoft in Russia. It marks a milestone in the maturity of the developing links between Microsoft Research, Microsoft Research Connections, and Moscow State University.”
Anton Konushin, head of the Vision Group at MSU, hopes that others can benefit from the Summer School. “Our school was truly a most selective one, with only one out of five students was accepted to the school. But with video lectures available online soon, we hope that this 400 students who hadn't made it to the event, can also become familiar with materials. We plan to make the influence of the school to Russian computer vision community a long-lasting one."
At the end of the week, students departed the summer school filled with enthusiasm and a deeper insight into how computer vision can change our world.