Abstract: T lymphocytes are vital components of the immune system in humans and other mammals. They are generated by multiple waves of blood cell precursors that migrate from the bone marrow to the thymus, where these multipotent precursor cells encounter signals that cause them to differentiate into T cells. This process is very illuminating as a model system to show how environmental signaling, endogenously expressed transcription factors, and epigenetic chromatin changes can work together in an orderly, stepwise process to convert cells efficiently from stem-like cells to useful differentiated cells. Powerful in vitro culture systems that mimic the thymus in an open format allow us to “zoom in” on the process, by enabling the developing cells to be observed, in real time down to clonal levels, and acutely manipulated at desired stages.
The Rothenberg lab has focused on answering three kinds of questions. First, how do the transcription factors in these cells act in an ordered cascade? Second, how does the epigenetic state of the chromatin affect what these transcription factors can do at a given stage, and how do the factors themselves alter each other’s actions to control differentiation transitions? Third, how do these mechanisms explain the high net efficiency but slow speed of this developmental process? The talk will show how recent results shed light on these questions.
Ellen Rothenberg is a Distinguished Professor of Biology at Caltech. Working at the interface between immunology, developmental biology, genomic molecular biology, and systems biology, she studies gene regulation and development of T lymphocytes, gene networks controlling hematopoietic cell fates, and mechanisms underlying the dynamics of single-cell developmental decisions. She graduated from Harvard University, earned her Ph.D. from Massachusetts Institute of Technology, and was a Jane Coffin Childs Postdoctoral Fellow at Memorial Sloan-Kettering Cancer Center. After an assistant research professorship at the Salk Institute for Biological Studies, she joined the Caltech faculty in 1982. She has been honored with teaching awards including the Richard P. Feynman Prize for Excellence in Teaching, and has been elected as Fellow of the American Association for the Advancement of Science, Fellow of the American Academy of Arts and Sciences, Distinguished Fellow of the American Association of Immunologists, and Member of the National Academy of Sciences.