Matt Good (UC, Berkeley)
Matt received a B.A. from UC Berkeley and a Ph.D. from the University of California San Francisco (UCSF) in Biochemistry. As a doctoral student in the laboratory of Professor Wendell Lim at UCSF he reconstituted the yeast mating MAPK pathway in vitro and determined the structure of kinase docking and scaffolding complexes, uncovering generalizable design principles in cellular signaling. He then began a Miller fellow position in the MCB department at UC Berkeley. Working jointly in the labs of Professor Rebecca Heald and Professor Daniel Fletcher, Matt development a cell-like system for interrogating important cell biological questions in vitro, including the size scaling relationships of cells and organelles. His current research program focuses on the cell size and shape dependence of intracellular assembly and signaling.
Adaptability of Intracellular Structures to Variations in Cell Size and Shape
Cells exist in a wide variety of shapes and sizes – from round eggs millimeters in diameter to highly elongated neurons with sub-micron extensions. Despite dramatic physical differences, growth and division of these cells is dependent on functional organelles, requiring that these intracellular structures adapt to a wide range of cell geometries. The mitotic spindle, a dynamic microtubule-based structure required for chromosome segregation, provides an important example of this flexibility. During Xenopus early embryo development, cell volume reduces nearly one million-fold due to division in the absence of growth, and spindle size scales with the spatial dimensions of the cell. However, an open question was whether cell size directly sets spindle size or whether compositional changes tied to a developmental program are necessary for size-regulation. The difficulty of modulating cell size in embryos presented a challenge to answering this question. As a postdoctoral fellow, I developed a cell-like system with controllable size to overcome this limitation. By combining droplet microfluidics and cell-free cytoplasmic extracts, I was able to generate spindle and nucleus structures inside compartments whose diameter can be tuned from microns to millimeters, recapitulating the spindle size-scaling trend observed during Xenopus embryogenesis. By modulating droplet diameter and geometry, I discovered that metaphase spindle size is intrinsically set by compartment volume, not shape, suggesting that limiting amounts of cytoplasmic material can restrict spindle growth. By extending this technology to other organelles, and characterizing how boundaries constrain biochemical processes, it should be possible to uncover additional principles of size regulation and identify new pathways that respond to cell size. The significance of this research lies in the intimate connection between cell size and embryo development, and the observation that cell and organelle size are often misregulated in disease.
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