John Franklin Enders University Professor
Chair, Department of Systems Biology
Kirschner Lab website
Executive Assistant: Meghan Van Orden
Investigating biological organization in space and time.
In the past, we have made significant contributions in three areas of fundamental biology: embryology, cell organization and cell cycle regulation. Each of these areas in different ways poses key questions regarding the coordination of biological events in space and time. A newer interest along the same lines is in cell size control. Our lab is unusually capable of developing quantitative, computational and theoretical methods that are applicable to a wide range of biological areas. This has given us an advantage in answering both old and new questions.
Three areas are particularly interesting to us at the moment.
Cell size. How do populations of cells maintain tight control over the variance in their cell size? We recently developed, or co-developed with collaborators, a number of new mathematical and biophysical methods for measuring cell size, and found clear evidence for size-dependent control of growth. We are now in an excellent position to identify the molecular mechanisms responsible for this.
Ubiquitin-mediated degradation. Our lab discovered the Anaphase Promoting Complex, which is responsible for the controlled degradation of cyclin through the ubiquitin/proteasome system at a specific point in the cell cycle. We now know of ~1,000 genes that are involved in the control of protein degradation in humans, but the functions of these genes are almost completely unknown. Very few targets of ubiquitin ligases have been identified, and very few proteins that are known to be degraded through the ubiquitin/proteasome system have been mapped to their cognate ligase. Again we have developed several new methods for connecting ligases and substrates. We are particularly interested in transcription factor degradation. We are also developing methods for identifying the “degradome” of a cell, which in some serious sense is the flip side of the transcriptome.
Gene expression and modulation of protein function in development. Although much is known about the conservation and variation in DNA and protein structure, the most important evolution happens at the level of developmental pathways and strategies. We have begun to look at comparative strategies of early development using transcriptomic time courses in Xenopus, sturgeon, and the hemichordate, Saccoglossus. We are keen to know whether these early programs are conserved or whether changes in early development presage later innovations and specializations. We now have an unprecedentedly powerful method for looking at transcription in single cells during developmental decisions. We are also working on new tools for studying changes in the proteome during development, in particular changes in post-translational modifications.
About Marc: Marc is a biochemist by training, but has always had a strong interest in using mathematics and physical principles to understand biology at a deeper level.
In 1993, Marc arrived at Harvard Medical School from the University of California, San Francisco, where he had served on the faculty as Professor for fifteen years, to become the Founding Chair of the Department of Cell Biology. In 2003, he again founded a new Department, the Department of Systems Biology. He and John Gerhart are co-authors of Cells, Embryos, and Evolution (Blackwell, 1997) and The Plausibility of Life: Resolving Darwin's Dilemma (Yale University Press, 2005).