Sydney Brenner supposedly opened a seminar that was meant to be a celebration of structural biology at the storied LMB by claiming: ‘I think we can all agree that hydrogen bonds and beta-pleated sheets are boring’. We remind ourselves of this legend whenever we discuss which of life’s mysteries we want to explore following the Resolution Revolution in cryo-EM. We can now determine atomic structures of just about anything, and often in multiple conformations, but we didn’t come here to collect structures. “Seeing is Forgetting the Name of the Thing One Sees” - and each of our projects started with this optimism: structural biology is discovery biology. Our efforts to resolve life’s molecular machinery will teach us how living matter works and, with some luck, may shed light on how living matter emerged.
In collaboration with a broad network of outstanding labs, our lab is making unique contributions to two fields of inquiry and the molcular connections between them. In the first field, we seek to to understand the homeostatic quality control mechanisms that determine whether ribosomes initiate message translation, and following initiation, whether they complete translation normally. When ribosomes fail to do so, we study how they abort translation and guide the degradation of aberrant protein syntheis products to preserve proteostasis. In the second field, we seek to understand the membrane biogenesis mechanisms that determine the shape, connectivity, topology and ultimately the functions of cells and intracellular organelles.
The sources of support for our work are listed below in chronological order since we started the lab in the summer of 2011. We wouldn’t be here without them and the vision they share with Mary Lasker (If you think research is expensive, try disease). The diversity in our sources of support and in the range of questions we are trying to answer is part design, part serendipity. Our lab believes in ecological edge effects: including increased dynamism, imagination and alternatives emerging in communities that have adapted to survive within the overlap between two or more habitats.