We are very excited to be hosting Professor James Rothman, Nobel Laureate, on 7 May, when he will deliver our Sherrington Prize Lecture. Professor Rothman will be speaking about New insights into basic mechanisms of synaptic neurotransmission.
Professor Rothman, the Sterling Professor of Cell Biology at Yale University, is one of the world's most distinguished biochemists and cell biologists. He is Chairman of the Yale School of Medicine’s Department of Cell Biology and is the Director and founder of the Nanobiology Institute.
Over his long and very distinguished career Professor Rothman has pushed forward to make new discoveries in various areas of research. Professor Rothman discovered key molecular machinery responsible for transfer of materials among compartments within cells, providing the conceptual framework for understanding such diverse and important processes as the release of insulin into the blood, communication between nerve cells in the brain, and the entry of viruses to infect cells. Numerous kinds of tiny membrane-enveloped vesicles ferry packets of enclosed cargo. Each type of vesicle must deliver its specialized cargo to the correct destination among the maze of distinct compartments that populate the cytoplasm of a complex animal cell. The delivery process, termed membrane fusion, is fundamental for physiology and medicine, as pathology in this process can cause metabolic, neuropsychiatric and other diseases. Rothman reconstituted vesicle budding and fusion in a cell-free system (1984) and discovered the complex of SNARE proteins (1993) which mediates membrane fusion and affords it specificity. He also uncovered the GTPase-switch mechanism which controls coated vesicle budding in the cell (1991).
Professor Rothman has also contributed to other fields. Together with DPAG’s Gero Miesenböck, he showed how patterns of synaptic activity in neural networks could be recorded optically using encoded synapto-pHlourins (1998). He discovered that hsp70’s are ATPases (1986) and peptide binding proteins (1989), thereby revealing how these molecular chaperones cycle on and off proteins to control their folding/unfolding. On theoretical grounds, he proposed (1981) that the role of the Golgi is to iteratively purify proteins, using its cisternae like plates in a distillation tower, an idea now implicit in all models of Golgi dynamics; and he provided the first evidence of sequential processing and vectorial transport across the stack (1981-1985).
Professor Rothman has received numerous awards and honours in recognition of his work on vesicle trafficking and membrane fusion, including the Nobel Prize in Physiology or Medicine in 2013. ON being given the award he was asked to reflect on his career, and he made a wonderful list of ‘Observations on style from a life in science’ which you can read in full on the Nobel website page here. Four of these are reproduced below.
Professor Rothman comments, ‘I will offer some observations that may be of interest to others, especially younger scientists. This is not necessarily to impart specific advice, which would be disingenuous as I rarely followed the advice I was given as a young man; it is more to offer the use of some of my personal experiences as a springboard for generalizations that may apply to the reader.’
-
Troubles Are Good For You (TAGFY). The “TAGFY Philosophy” was first enunciated by the master enzymologist Ephraim Racker, and I pass it on. TAGFY has proven true for me over and over again. For example, after Erik Fries and I first published cell-free transport, we had great difficulty repeating our exact results, and it would have been easy to be discouraged. But TAGFY meant that we were really about to discover something basic that we had no idea about. Indeed, in resolving the “trouble” we found that we had reconstituted intra-Golgi vesicular transport, a process not previously known to exist (as documented in the Nobel Lecture). TAGFY can give you strength in hard times.
- If you are hitting your head against a brick wall, find a new wall. It is so human to try that experiment one more time hoping for a better result. It almost never pays. Try a new approach. Remarkably, most people don’t.
- It is much harder to stop a project than to start one. To do so takes real intellectual honesty and a complete disregard of ego. Worse, stopping involves a huge sunk cost of time and emotion, but if you don’t, then the next phase (which may hold success) will be only further away.
- Don’t be afraid to be “stupid.” If you don’t understand it, it is probably unclear. If you don’t know how to do something, ask. It is far better than losing days in the lab because you didn’t. It is amazing how many people don’t ask. I always did and it made a difference.