Research Projects
I am interested in the application of
topology and geometry to understand biological processes.
The Tangle Model
In the last few
years I have studied the tangle model for site-specific recombination. The
tangle model is a mathematical method due to De Witt Sumners
and Claus Ernst [D.
W. Sumners, C. Ernst, S. J. Spengler, N. R. Cozzarelli. Quart. Rev. Biophysics 28, 3
(1995), 253 - 313;
In my PhD dissertation (advisor De Witt Sumners; abstract) I
applied the tangle model (based on knot theory and low-dimensional topology) to understand the mechanism used by some enzymes to change
the geometry and topology of the DNA. I focused in the two following systems:
Gin from bacteriophage
Mu.
Xer from Escherichia
coli.
The DNA knots and/or links produced by Gin or Xer recombination on circular DNA substrates were characterized by Roland Kanaar (Gin recombination), by Nancy Crisona (mutant Gin recombination) in Nicholas Cozzarelli's lab in Berkeley (Gin recombination), and by Jonathan Bath and Sean Colloms in David Sherratt's lab in Oxford (Xer recombination). When I analyze these data, I translate the biological problem into a mathematical problem using the mathematics of 2-string tangles.
While at Berkeley, I have continued the Xer work in collaboration with De Witt Sumners and Sean Colloms. I also worked
with an undergraduate research assistant, Yuki Saka, on a computer
implementation of the tangle model. The resulting software, TangleSolve, is available
for use on the web or for download. More recently, jointly with John
Luecke and Isabel Darcy, we
have done a knot theoretical analysis of the Mu transpososome (paper in
preparation).
In the last few years, I have been working on modeling unknotting by type II
topoisomerases. This project was inspired by our work on DNA packing in
bacteriophages (Arsuaga et al. 2002), and
took off as an undergraduate project first with Barath
Raghavan (now a graduate student at UCSD), then Diana Nguyen (entering UCLA
Medical School), Miki Suga (just graduated) and finally, Xia (Carol) Hua (senior
- Hong Kong University). Our first paper was just submitted for publication
(pre-print PDF).
Radiation Research:
When I came to Berkeley I joined the Mathematical Radiobiology group led by Professor Rainer Sachs. Our group consists of one senior investigator, two postdocs, one graduate student and several undergraduate assistants. We develop mathematical and biophysical models of repair in human cells by analyzing the aberrations induced on them by low-dose ionizing radiation. We use Monte-Carlo simulation to give a quantitative analysis of various models for chromosomal aberration production. This analysis is compared to experimental data given by mFISH (multiplex fluorescence in situ hybridization). Most of our results have been published; the relevant papers can be found in the list of publications.
