ChEBE Faculty Research
Laurence Brewer, Ph.D.
Assistant ProfessorDr. Brewer is an affiliate faculty member of the School of Molecular Biosciences and a participating member of the Center for Reproductive Biology.
School of Chemical Engineering and Bioengineering Office: EME 49 (Tel: 509 335-1888) Graduate StudentsLaura Cree |
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Research Interests
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Single molecule force spectroscopy
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Spermiogenesis
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Multichannel flow cells
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The broad area of research studied by the Brewer lab is chromatin remodeling in eukaryotic systems. We measure changes in the structure of individual DNA molecules as they are exposed to proteins or enzymes in microfluidic cells that mimic in-vivo cellular processes. The instrumentation that we design and build for our experiments features optical traps that measure changes in the tension and position of single DNA molecules at the piconewton and nanometer level. We are particularly interested in utilizing techniques from the physical sciences to discover novel ways to investigate the complicated machinery of the cell.
The sperm genome is a unique model eukaryotic system to study. The fractional volume taken up by the genome in the nucleus of the cell is approximately 13%, similar to that of DNA in viruses, and demands that the DNA be packaged at near crystalline density. Because of this the majority of histones are displaced from sperm chromatin (85% in humans) during a process called spermiogenesis and the fundamental unit of chromatin is remodeled into a 50 kb donut shaped toroid. We are specifically interested in determining the molecular mechanisms that allow this remarkable transformation to take place. We use both fluorescence microscopy and force spectroscopy to to measure mechanical and topological changes in single DNA molecules due to the binding of sperm nuclear proteins.
DNA structures shaped like toroids are found not only in the sperm cell but also in viruses and nucleosomes. The formation of all of these structures is similar in that they are shaped by electrostatic interactions between loops of DNA. They differ in that the interaction between loops of DNA can be either attractive, such in the sperm nucleus, or repulsive, such as in viruses.
Understanding how spermiogenesis takes place is important for understanding male infertility, abnormal embryo development and spontaneous abortion.
Biographical Information
Dr. Brewer received degrees in physics from Yale (B.S., 1978) and M.I.T. (Ph.D., 1985). His post-doctoral position (1985-1987) was at the National Bureau of Standards in Boulder, Colorado where he studied the laser-cooling of trapped atomic ions to mK temperatures to create strongly coupled plasmas. In the mid-1990’s, while at Lawrence Livermore National Lab, he became interested in applying techniques utilizing lasers to trap individual DNA molecules and study fundamental cellular processes in-vitro. He was appointed an assistant professor in the School of Chemical and Bioengineering in 2007.
Selected Publications
1. Leuba, S., Brewer, L. Chromatin Structure and Dynamics (2008) in Single Molecule Biology (in press, ed. Alex Knight, Elsevier).
2. Brewer, L., Bianco, P. Laminar flow cells for single molecule studies of DNA-protein interactions (2008) Nature Methods 5, 517-525.
3. 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.
4. 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.
5. Brewer, L., Corzett, M., Balhorn, R. Condensation of DNA by spermatid basic nuclear proteins (2002) J Biol Chem 277, 38895-900.
6. 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.
7. 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.
8. Brewer, L.R., Corzett, M., Balhorn, R. Protamine-induced condensation and decondensation of the same DNA molecule (1999) Science 286, 120-3.
9. Brewer, L.R., Davidson, J.C., Balch, J.W., Carrano, A.V. Three-dimensional imaging of DNA fragments during electrophoresis using a confocal detector (1995) Electrophoresis 16, 1846-50.
10. Brewer, L.R., Davidson, J.C., Balch, J.W. Three-dimensional imaging of DNA fragments during electrophoresis using a confocal detector (1995) Ultrasensitive Instrumentation for DNA Sequencing and Biochemical Diagnostics, Gerald E. Cohn et.al. Editors, SPIE 2386, 86-96.
11. Brewer, L.R. Suppression of Beam Steering in an Injection-Locked Laser Diode Array (1991) Applied Physics Letters 59, 3078-3080.
12. Brewer, L.R. Highly Coherent Injection-Locked Laser Diode Arrays (1991) Applied Optics 30, 317-320.
13. Brewer, L.R., Buchinger, F., Ligare, M., Kelleher, D. E. Resonance-enhanced multiphoton ionization of atomic hydrogen (1989) Physical Review. A 39, 3912-3923.
14. Itano, W.M., Brewer, L.R., Larson, D.J., Wineland, D.J. Perpendicular laser cooling of a rotating ion plasma in a Penning trap (1988) Physical Review. A 38, 5698-5706.
15. Brewer, L.R. et al. Static properties of a non-neutral 9Be+ ion plasma (1988). Physical Review. A 38, 859-873.
16. Bollinger, J.J., Brewer, L.R., et. al. Ion trapping techniques: laser cooling and sympathetic cooling in Intense Positron Beams (ed. E.H. Ottewitte, W. Kells) (World Scientific Press, Singapore, 1988).
17. Brewer, L.R., Prestage, J. D., Bollinger, J.J., Wineland, D.J. A high Γ, strongly coupled, nonneutral ion plasma. In Strongly Coupled Plasmas (ed. Rogers, F., DeWitt, D) (Plenum Press, 1987).
18. Kelleher, D.E., Ligare, M., Brewer, L.R. Resonant four-photon ionization of atomic hydrogen (1985) Physical Review. A 31, 2747-2749.