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RESEARCH INTERESTS: Chromatin remodeling during spermiogenesis. RESEARCH SUMMARY: Spermiogenesis is the final stage of development of the sperm cell and occurs in a remarkable series of transformations that expel 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 each sperm nuclear protein plays to remodel, compact, and protect the genome during spermiogenesis. Currently we are studying the role that biomechanical forces play during genome compaction. This research is important for understanding male infertility, abnormal embryo development and spontaneous abortion. REPRESENTATIVE PUBLICATIONS 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. Brewer, L., Corzett, M., Balhorn, R. Condensation of DNA by spermatid basic nuclear proteins (2002). J Biol Chem 277, 38895-900. Bianco, P. R., Brewer, L.R., Corzett, M., Balhorn, R., Yeh, Y., Kowalczykowski, S.C., Baskin, R.J. Processive translocation and DNA unwinding by individual RecBCD enzyme molecules (2001) Nature 409, 374-8. Balhorn, R., Brewer, L., Corzett, M. DNA condensation by protamine and arginine-rich peptides: analysis of toroid stability using single DNA molecules (2000) Mol Reprod Dev 56, 230-4. Brewer, L.R., Corzett, M., Balhorn, R. Protamine-induced condensation and decondensation of the same DNA molecule (1999) Science 286, 120-3. |
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