A pioneer in the study of the three-dimensional structure of the genome, Job Dekker, PhD, professor of biochemistry & molecular pharmacology and co-director of the Program in Systems Biology, was named a Howard Hughes Medical Institute (HHMI) investigator. Dr. Dekker, developer of the chromosome conformation technologies used to map the topography of the genome, was one of 26 scientists chosen for his scientific excellence from a pool of 894 applicants. Over the next five years, HHMI has committed $153 million to support these innovative scientists.
“This is one of the most prestigious and sought-after scientific awards in the world. The Howard Hughes Medical Institute recognizes exceptionally creative thinkers and innovative scientists who are at the forefront of expanding the boundaries of scientific knowledge,” said Chancellor Michael F. Collins. “This award allows Dr. Dekker the freedom to pursue novel ideas that can fundamentally change our understanding of disease. All of us at UMMS are incredibly proud of what he has accomplished.”
“It is a tremendous honor to be named among such an accomplished group of scientists,” said Dekker. “Being an HHMI investigator provides us with the resources to pursue game-changing questions about how chromosome structure affects disease formation. With this support we’ll be able to investigate high-risk, high-reward research, such as the kind that led to the initial development of chromosome conformation capture technology.”
Although DNA is comprised of a linear sequence of bases, it doesn’t exist inside the cell nucleus in a simple, straight form. More like a ball of cooked spaghetti, the genome folds and loops back on itself so it can fit inside the tight confines of the nucleus. How the genome is packed inside the nucleus is tightly controlled and varies from cell type to cell type. And each unique shape has a profound influence on which genes in a cell are turned on or turned off.
Seeking tools and technology for mapping the three-dimensional structure of the genome in detail, Dekker developed a biochemical technique for determining how DNA segments interact and are linked to one another. The result, akin to a “molecular microscope,” can be used to detect physical interactions between DNA segments. The more interactions between segments, the more closely associated in space they are, due to chromosome folding. This breakthrough discovery was the genesis of what are now termed “3C,” “5C” and “Hi-C” tools, used by researchers worldwide interested in mapping the structure and organization of chromosomes inside cells.
“Before 3C, we could see that genomes looked different across cell types, but limitations in imaging technologies meant we couldn’t study these differences in a meaningful way,” said Dekker. “Chromosome conformation capture technologies have rapidly taken hold and allowed our lab and others to explore the structure of the genome in a way that wasn’t previously available to scientists.”
Since joining UMMS, Dekker has refined and enhanced the initial chromosome conformation techniques to visualize whole genomes, combining it with next-generation sequencing to create high through put versions.
Dekker has made a number of key discoveries related to how the structure of a genome may influence genetic function and contribute to human disease. Included among these discoveries is the identification of a new mechanism involving chromatin loops that is responsible for controlling genomic structure and activating genes to generate specific cell types. He has also found that chromosomes fold in a series of contiguous “yarns” that harbor groups of genes and regulatory elements, bringing them in contact with each other and allowing them to work in a coordinated manner during development. Recently Dekker and co-workers also uncovered how chromosomes are condensed inside mitotic chromosomes, which are among the most iconic structures in the cell.
In 2012, a team led by Dekker offered conclusive evidence that the three-dimensional structure of the chromosome strongly influences patterns of chromosome rearrangements and translocations, shedding light on a fundamental process related to cancer and our understanding of cancer genomics.
A member of the UMMS faculty since 2003, Dekker received his doctoral degree in biochemistry from Utrecht University in the Netherlands. He trained as a postdoctoral fellow at Harvard University with Nancy Kleckner, PhD, studying chromosome structure and developing the techniques that led to the 3C technology.
Dekker was elected to the American Association for the Advancement of Science in 2014. In 2007, he was named a Keck Foundation Distinguished Young Scholar in Biomedical Research, and he received the 2011 ASBMB Young Investigator Award from the American Society of Biochemistry and Molecular Biology.
HHMI encourages its investigators to push their research fields into new areas of inquiry. By employing scientists as HHMI investigators—rather than awarding them research grants—HHMI gives scientists the freedom to explore and, if necessary, to change direction in their research. Moreover, they have support to follow their ideas through to fruition—even if that process takes many years.
“Scientific discovery requires original thinking and creativity,” says HHMI President Robert Tjian. “Every scientist selected has demonstrated these qualities. One of the most important things we can do at HHMI is to continue to support and encourage the best discovery research. We don’t know this for certain, but the ideas that emerge from these labs might one day change the world, and it’s our privilege to help make that happen.”
HHMI will provide each investigator with his or her salary, benefits and a research budget over an initial five-year appointment. The Institute will also cover other expenses, including research space and the purchase of critical equipment. HHMI appointments may be renewed for additional five-year terms, contingent on a successful scientific review.
Mid-career researchers with five to 15 years of experience as faculty members at more than 200 institutions were eligible to apply. Applications from the 894 eligible applicants were evaluated by distinguished biomedical researchers, who narrowed the field to 59 semifinalists. The semifinalists attended a scientific symposium at HHMI’s Janelia Research Campus in April and presented a brief research talk to members of the review panel. The 26 new HHMI investigators were selected shortly after the scientific symposium.
Through its flagship HHMI Investigator Program, the Institute has joined with more than 70 distinguished U.S. universities, hospitals, institutes and medical schools to create an environment that provides flexible, long-term support for approximately 330 Hughes investigators and members of their research teams. HHMI investigators are widely recognized for their creativity and research accomplishments: 182 HHMI investigators are members of the National Academy of Sciences and there are currently 17 Nobel laureates within the investigator community.
Dekker joins six other HHMI Investigators at UMMS: Roger J. Davis, PhD, the H. Arthur Smith Chair in Cancer Research and professor of molecular medicine and biochemistry & molecular pharmacology; Marc R. Freeman, PhD, professor of neurobiology; Michael R. Green, MD, PhD, the Lambi and Sarah Adams Chair in Genetic Research and professor and chair of molecular, cell & cancer biology; 2006 Nobel Laureate Craig C. Mello, PhD, the Blais University Chair in Molecular Medicine and distinguished professor of molecular medicine and cell & developmental biology; Melissa J. Moore, PhD, the Eleanor Eustis Farrington Chair in Cancer Research and professor of biochemistry & molecular pharmacology; and Phillip D. Zamore, PhD, the Gretchen Stone Cook Chair of Biomedical Sciences and professor of biochemistry & molecular pharmacology.