For his novel approach to creating maps that enable researchers to zoom in on the human genome and reveal features of DNA structure inside the nucleus, Erez Lieberman Aiden has been named the 2011 Grand Prize winner for the GE & Science Prize for Young Life Scientists. The annual competition includes a grand prize award of $25,000 and is supported by GE Healthcare and the journal Science.
How does the 2-meter long human genome fold up inside the nucleus of a cell? Aiden, a fellow at the Harvard Society of Fellows and visiting faculty at Google, developed a method for three-dimensional genome sequencing that seems to answer this question. He and his team pioneered the technique, known as Hi-C, and deployed it to create “the first genome-wide spatial map of the human genome,” he explained.
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This movie shows a genome fractal globule unravelling locally, making genetic information in the target region highly accessible.
As a student in the Lander lab at MIT, Aiden worked with Nynke van Berkum to develop a new method for determining the 3-D structure of nuclear DNA, and discovered that the human genome folds into a dense, unknotted structure known as the fractal globule.
“In graduate school, one of the things I hoped to learn more than anything was how molecular biology and sequencing can be coupled in order to help us dissect the internal machinery of cells,” said Aiden.
Aiden, also a regional winner from North America, will receive the award for his research in the field of molecular biology in Stockholm, Sweden, during a 9 December ceremony. He received the grand prize for his essay, “Zoom!”, published in the 2 December issue of Science.
“This is a huge honor for myself and my collaborators,” Aiden added. “I am especially indebted to my advisor, Eric Lander, and to Andreas Gnirke for their mentorship, as well as to my principal collaborator, the extraordinarily talented Nynke van Berkum.”
“It is a privilege to recognize and reward these promising early-career doctoral students across the globe for their tremendous achievements in molecular biology,” said Monica Bradford, executive editor of Science. “We are excited to honor researchers who give us inspiration and contribute novel findings to science, which may have implications for society.”
Erez Lieberman Aiden’s prize-winning essay demonstrates that it is possible to transform a DNA sequencer into a “camera” to determine how the human genome is folded inside the nucleus of a cell. By using Hi-C, the three-dimensional sequencing method, Aiden and his colleagues found that active and inactive portions of the genome are separated inside the nucleus.
“It is well known that local chemical modifications, to both nucleotides and the histone proteins that package them, play an important role in genetic regulation,” explained Aiden. “The segregation of active and inactive genomic regions that we report is a ‘spatial epigenetic mark’ that suggests that the genome’s fold also plays a role in turning genes on and off, a sort of ‘epigenetics via origami.’”
“Our data at the megabase scale is consistent with a fractal globule, an extraordinarily dense, but entirely unknotted, configuration,” he added. Aiden finds that the fractal globule configuration is interesting because the polymer is in an unknotted state, possibly providing “an answer to how an extraordinary amount of genetic material is packed into the cell nucleus (only a few microns wide), while keeping the information it contains accessible to the cell.”
The study also has some interesting implications for physicists, he added. “Theorists had proposed that ‘fractal globule’ polymers might exist, but this is the first observational evidence for the existence of such a state in any polymer. It’s radically different from the equilibrium globule, the classic model of a condensed polymer.”
Aiden grew up in New York City and studied mathematics, physics, and philosophy at Princeton University. He received a Ph.D from Harvard and MIT, where he was advised by Eric Lander and Martin Nowak. Aiden has received the National Institutes of Health New Innovator Award, the American Physical Society’s Award for the Best Doctoral Dissertation in Biological Physics, and the Lemelson-MIT student prize, given to the best student inventor at MIT.
Aiden has also developed a new, quantitative approach, together with Jean Baptiste Michel at Harvard University, for the analysis of culture using digitized books.
Each year since 1995, the GE & Science Prize for Young Life Scientists has recognized innovative young molecular biologists at an early stage of their careers. Some 69 regional winners and 17 grand prize winners have so far received the award, honoring exceptional thesis work in the field of molecular biology.
Applicants for the 2011 GE & Science Prize for Young Life Scientists earned their Ph.D degrees in 2010 and submitted a 1000-word essay based on their dissertations. Their essays were judged on the quality of research and the applicants’ ability to articulate how their work would contribute to the field of molecular biology, which investigates biological processes in terms of the physical and chemical properties of molecules in a cell.
A judging panel selects the GE & Science Prize for Young Life Scientists grand prize winner and presents regional awards in four geographic regions: North America, Europe, Japan, and all other countries. The regional winners receive $5000 awards.
“All four winners have made important contributions that advance our knowledge of cell biology at the molecular level,” said Kieran Murphy, president and chief executive officer of GE Healthcare Life Sciences. “As part of our wider undertaking to support research that will increase our understanding of disease mechanisms, we’re proud to recognize and reward these outstanding young life scientists.”
In addition to the grand prize and regional winner from North America, the 2011 awards also recognize the following regional winners:
Felipe Teixeira (Europe): For his essay, “Mechanisms of Transgenerational DNA Methylation Inheritance.” Teixeira was born in Rio de Janeiro, Brazil. He received his bachelor of science degree in biological sciences and a master of science degree in genetics from the Federal University of Rio de Janeiro. Teixeira completed his Ph.D (University of Paris XI) under the supervision of Vincent Colot, first at the Unité de Recherche en Génomique Végétale (Evry, France) and then at the École Normale Supérieure (Paris, France). His research work focused on the mechanisms of transgenerational DNA methylation inheritance in Arabidopsis. Teixeira is now a postdoctoral fellow in Ruth Lehmann’s lab at the New York University Medical Center/Skirball Institute, where he is studying the mechanisms involved in the regulation of transposable elements during Drosophila germline development.
“I have always been fascinated by the mechanisms involved in the inheritance of genetic information across generations,” said Teixeira. “During my Ph.D. training, I studied the inheritance patterns of a classic epigenetic mark—DNA methylation—in plants. This modification plays key roles in the control of genome activity in plants and mammals, and therefore must be tightly regulated. Our findings uncovered the existence of a previously unknown RNA interference (RNAi)-based corrective mechanism that protects the genome against transgenerational epigenetic defects.”
Tatsuya Tsukahara (Asia): For his essay “CDK Directs the Chromosome Passenger Complex to Centromeres for Chromosome Bi-Orientation.” Tsukahara was born in Japan and graduated from the University of Tokyo in 2005. He conducted his Ph.D work in the laboratory of Yoshinori Watanabe at the Institute of Molecular and Cellular Biosciences, University of Tokyo, where he studied the molecular mechanism of faithful chromosome segregation using fission yeast and human cells. Tsukahara is currently an assistant professor in the laboratory of Hiroyuki Takeda at the Graduate School of Science, University of Tokyo. He has moved into the field of developmental biology and is studying the epigenetic regulation of vertebrate development and differentiation using medaka fish.
“My study revealed that Cyclin-dependent kinase (CDK) promotes the chromosome bi-orientation, an essential event for faithful chromosome segregation, through direct phosphorylation of Chromosome Passenger Complex (CPC),” said Tsukahara. “Because CDK, CPC, and the chromosome segregation error are known to be involved in generation or progression of cancers, this finding may open the way for the development of novel cancer diagnosis or anti-cancer drugs.”
Eran Eden (all other countries): For his essay, “Proteome Dynamics and the Fate of Individual Cancer Cells in Response to a Drug.” Eden was born in Haifa, Israel, and received a bachelor of science degree in computer science from the Technion-Israel Institute of Technology. Following a student exchange visit to the Center for Biological Sequencing in Denmark, he became fascinated with molecular biology and returned home to pursue a bachelor’s degree in biology and a master’s degree in computer science at the Technion. His Ph.D research, conducted under the guidance of Uri Alon at the Weizmann Institute of Science in Rehovot, Israel, focused on the proteome dynamics and half-lives of individual living human cancer cells. Since completing his Ph.D, Eden co-founded MeMed Dx, a startup company in the field of personalized diagnostics of infectious disease.
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The American Association for the Advancement of Science (AAAS) is the world’s largest general scientific society, and publisher of the journal, Science as well as Science Translational Medicine and Science Signaling. AAAS was founded in 1848, and includes 262 affiliated societies and academies of science, serving 10 million individuals. Science has the largest paid circulation of any peer-reviewed general science journal in the world, with an estimated total readership of 1 million. The non-profit AAAS is open to all and fulfills its mission to “advance science and serve society” through initiatives in science policy, international programs, science education, and more. For the latest research news, log onto EurekAlert!, the premier science-news Web site, a service of AAAS.
Read the full text of essays by the winners and learn about applying for next year’s awards.
Learn more about the GE & Science Prize for Young Life Scientists.