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Research Interests
1) Chromatin remodeling, chromatin architecture and cell
shaping during spermiogenesis
2) Unpacking and remodeling the sperm genome during
fertilization.
Research Summary
Spermiogenesis is the final stage of development of the sperm cell and occurs in a remarkable series of transformations that displace histones from sperm chromatin and repackage the DNA into donut-shaped protamine-DNA toroids. This serves to both inactivate and protect the genome. In my laboratory, we study spermiogenesis in mammals by measuring changes in the structure of single DNA molecules as they are exposed to sperm nuclear proteins in microfluidic cells that mimic in-vivo cellular process. This allows us to observe changes in the DNA structure in real time, without the complications of aggregation and precipitation that occur using bulk biochemistry techniques. The instrumentation that I design and build for my experiments features optical traps that both manipulate and measure changes in the tension and position of single DNA molecules at extremely sensitive levels (pN and nm). We are interested in understanding the role that the sperm nuclear proteins play to remodel, compact, and protect the genome during spermiogenesis. Currently we are studying the role that biomechanical forces play during genome compaction and cell shaping. This research is important for understanding male infertility, abnormal embryo development and spontaneous abortion.
Research Publications
Brewer, L., Bianco, P. Laminar flow cells for single-molecule studies of DNA-protein interactions (2008) Nat. Methods 5, 517-525.
Leuba, S., Brewer, L. Chromatin Structure and Dynamics (2008) in Single Molecule Biology (in press, Ed. Alex Knight, Elsevier)
Brewer, L., Corzett, M., Lau, E.Y., Balhorn, R. Dynamics of Protamine 1 Binding to Single DNA Molecules (2003) J Biol Chem 278, 42403–42408.
Brewer, L.R., Friddle, R., Noy, A., Baldwin, E., Martin, S.S., Corzett, M., Balhorn, R., Baskin, R.J. Packaging of Single DNA Molecules by the Yeast Mitochondrial Protein Abf2p (2003) Biophy J 85, 2519-2524.