Reverse Engineering of Biological Circuits Underlying Aging and Development

Marc Kirschner’s lab is taking a large-picture, systematic approach to understanding the biology of early development and of aging, two processes that bookend our lives and the lives of all living creatures. Typically, development and aging are studied in separate research fields, but Kirschner aims to use systems biology and machine learning approaches to uncover the cellular circuitry that drive each and to better understand where they might overlap, using as a model the small crustacean Daphnia magna, also known as the water flea.

Affiliated Investigators

Marc Kirschner, Ph.D.

Harvard Medical School

Marc Kirschner has made major contributions to several areas of fundamental biology: embryology, cell organization, cell cycle regulation, evolution, and systems biology. In embryology, Kirschner studied the molecular basis of timing of embryonic events in early development. He discovered the mid-blastula transition, in which embryos make an abrupt transition from compressed cell cycles with virtually no transcription to a slower, complex cell cycle with massive transcription. Studying a later stage of development, his laboratory characterized the first embryonic inducer, where Kirschner developed the use of dominant negative proteins. His work on the cytoskeleton involved important discoveries in microtubules, actin filaments and nuclear lamins. His laboratory discovered the dynamic instability of microtubules, the distinct mechanism and role of GTP in microtubule assembly, and the protein tau, which regulates microtubule polymerization and is a major causal component of certain neurodegenerative diseases. In the actin field, he characterized the regulation of two major actin polymerization machines, the N-WASP and WAVE complexes. His work on the cell cycle, principally using biochemical methods in frog egg extracts, was key to establishing the basic cyclin/cdk1-based autonomous oscillator at work in all eukaryotic cells. In the course of that work, he identified and purified the anaphase promoting complex and its associated E2 enzymes that regulate the degradation of mitotic proteins and showed that one of them, securin, acts to hold the sister chromosomes together. In the course of those studies, he helped characterize the complex molecular machinery of the spindle assembly checkpoint, a circuit that arrests mitosis when there is spindle damage. In studies of evolution, he is best known for exploring the cellular and developmental basis for evolvability, and he co-authored two books with John Gerhart. His work in systems biology has focused on quantitative models on Wnt signaling and the fold change response in the Wnt pathway. Kirschner is a member of the National Academy of Sciences and the American Academy of Arts and Sciences, a Foreign Member of the Royal Society of London and the Academia Europaea. He has received numerous honors and awards.