Despite a vast knowledge of molecules in biology, we know very little about how to build cells. While there is no shortage of schematic diagrams suggesting how molecules in a particular process interact, where they go, and what they do, very few of these cellular processes have actually been built from their molecular parts. Perhaps this is not surprising given that the equipment in molecular biology labs – sonicators, centrifuges, and chromatography columns – is primarily aimed at separating molecules rather than putting them back together. Control of assembly is an engineering problem.
The Fletcher Lab uses a combination of bottom-up and top-down approaches to understand how biological systems are built, how they break, and what to do to fix them. Through in vitro reconstitution and experiments with live cells, we are linking the behavior of a system with the properties of its molecular parts, discovering general principles that control assembly of biological structures, and identifying strategies for therapeutic intervention. By developing custom experimental methods to control and quantify the assembly of cellular structures and tissues, we are adding what has been lost in the sonicator, centrifuge, and chromatography column – the physical constraints and boundary conditions that shape the structures and dynamics of cells.
In Vitro Reconstitution
How are cell-sized structures built from molecular-sized parts?
We take a bottom-up approach to studying the spatial organization and function of cell membranes and the cytoskeleton. Using purified proteins and cytoplasmic extracts, we develop methods for reconstituting cellular processes in vitro, paying special attention to the physical constraints the structures experience in cells.
How do cells and tissues sense, process, and respond to physical inputs?
Physical forces and mechanical properties of a cell’s surroundings can alter cellular behavior in dramatic ways. We study the phenomenology of mechanotransduction in health and disease, with the goal of discovering how force is converted into the biochemistry that regulates cell behavior.
Imaging & Biomedical Instrumentation
How do we measure what we want to measure where, when, and how we want to measure it?
Optical microscopy, force microscopy, microfabrication, and microfluidics provide the opportunity to monitor and manipulate biological assembly. When existing approaches don’t allow us to measure what we need to measure, we develop new methods. Our work on optical microscopy has led to low-cost diagnostic technologies for global health (CellScope) and an introductory optics instructional kit.
The Fletcher Lab @ UC Berkeley is part of the QB3 Institute and part of the Department of Bioengineering. We are also affiliated with the Department of Molecular and Cell Biology and the Physical Biosciences Division of Lawrence Berkeley National Laboratory (LBNL), as well as the Blum Center and Center for Information Technology Research in the Interest of Society (CITRIS).
The students and researchers in our lab are part of the UC Berkeley/UCSF Graduate Program in Bioengineering, the UC Berkeley Biophysics Graduate Group, the UC Berkeley Nanoscale Science and Engineering Graduate Group, and various departments and programs at UC Berkeley and UCSF, including MD/PhD and MD/MPH.