Dr. Brewer is a physicist with a background in laser cooling and trapping of atoms, atomic spectroscopy and optical science, who has recently started to experimentally study the condensation of single, optically trapped, DNA molecules by proteins. These experiments have been pursued in collaboration with a structural biologist at Lawrence Livermore National Laboratory (LLNL) - Dr. Rod Balhorn - and have been carried out in Dr. Brewer's laboratory at LLNL. While this collaboration has been successful, and recently resulted in publications in various journals, including Science, Dr. Brewer has not been able to propose which research questions to pursue because of his lack of a fundamental knowledge of biology. While he is adept at building optical traps and imaging single DNA molecules, he is in large part dependent on Dr. Balhorn for determining which direction the research should take. Dr. Brewer's immediate objective is to gain the necessary biology knowledge to both understand, and propose questions in the field he is studying - the structural biology of mammalian gamete cell- and his long term career goal is to become an independent researcher in the field of biomedicine, applying experimental physics techniques to study biological questions. His career development plan is to take courses in the Molecular and Cellular Biology department at U.C. Berkeley for two years, learn laboratory protocols and techniques relevant to his proposed research from Dr. Balhorn's group, and simultaneously pursue experiments in his own laboratory, in collaboration and consultation with his proposed mentor, Dr. Balhorn. The research proposed is to study the sequence of proteins that condense DNA in the developing mammalian sperm cell and decondense it following fertilization. An individual, optically trapped DNA molecule will be moved sequentially through the proteins in a novel multichannel flow cell, and structural changes in the molecule will be observed by fluorescence microscopy. The proteins include the transition proteins TP1 and TP2, the condensing proteins, protamine 1 and 2, and the decondensing protein nucleoplasmin. The results of this research have a direct bearing on understanding male infertility.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Mentored Quantitative Research Career Development Award (K25)
Project #
1K25HD001387-01
Application #
6166910
Study Section
Pediatrics Subcommittee (CHHD)
Program Officer
Taymans, Susan
Project Start
2000-09-01
Project End
2005-08-31
Budget Start
2000-09-01
Budget End
2001-08-31
Support Year
1
Fiscal Year
2000
Total Cost
$154,572
Indirect Cost
Name
Lawrence Livermore National Laboratory
Department
Engineering (All Types)
Type
Organized Research Units
DUNS #
827171463
City
Livermore
State
CA
Country
United States
Zip Code
94550
Brewer, Laurence R; Bianco, Piero R (2008) Laminar flow cells for single-molecule studies of DNA-protein interactions. Nat Methods 5:517-25
Brewer, Laurence; Corzett, Michele; Lau, Edmond Y et al. (2003) Dynamics of protamine 1 binding to single DNA molecules. J Biol Chem 278:42403-8
Brewer, Laurence; Corzett, Michele; Balhorn, Rod (2002) Condensation of DNA by spermatid basic nuclear proteins. J Biol Chem 277:38895-900