Expertise:
- Hydrodynamic and thermodynamic modeling: Using tools such
as analytical ultracentrifugation and dynamic light scattering my
research group focuses on the elucidation of structure and function of
biological systems. To this end, I combine modern numerical methods and
computational approaches, including parallel distributed computing, to
develop new methodologies for analyzing and fitting experimental data
from these hydrodynamic techniques. This long-time effort has resulted
in the creation of the UltraScan software suite. By creating this
software my goal is to implement these new methods in a user-friendly
data analysis environment so that the methods can be applied by any
investigator, even those without extensive expertise in computing,
mathematics or biophysics. A major emphasis in developing these new
methods is placed on the global approach, which takes advantage of
the added information content of multiple datasets from different
experimental methods and experimental conditions. The global approach
presents new challenges with respect to optimization algorithms and
requires new paradigms to deal with the large amounts of data included
in the global approach. To further improve the information derived from
the global approach I have started to integrate multiple biophysical
techniques such as sedimentation velocity, sedimentation equilibrium,
as well as Raleigh and dynamic light scattering for a global analysis of
complex systems. Now I am developing novel analysis methods utilizing
the latest advances in technology and instrumentation. Among them are
parallel computational approaches using Linux Beowulf systems. Such
tools are required to model the large and computationally demanding
systems of experimental data in a global approach.
- Local and Global Optimization algorithms: As part of the
creation of new algorithms for the UltraScan software, I am focusing
on improving the stability and robustness of numerical optimization in
the fitting algorithms. I am exploring the use of genetic algorithms
and a multidimensional spectrum analysis to obtain a multivariate
optimization of finite element solutions to globally modeled sedimentation
experiments. Mathematical modeling of hydrodynamic processes allows us
to compare the efficiency, speed and robustness of both deterministic,
gradient based approaches as well as stochastic approaches. Our goal is
to model distributions of macromolecular assemblies, mixtures and systems
that are heterogeneous in both shape and molecular weight. Algorithm
design includes both the development of new adaptive finite element
solutions to the Lamm equation, a second order partial differential
equation used to model sedimentation and diffusional transport, and the
development of parallel optimization strategies. Several of these methods
employ stochastic approaches to assist with issues in signal processing
and signal amplification. Another area of research involves parsimonious
regularization for satisfying Occam?s razor when unique solutions do not
exist, a problem encountered in multivariate optimization of noisy data.
- High-Performance Grid Computing: An integral area of interest
for my research is the application of high-performance networking to grid
computing applications which ties multiple supercomputers together into
a single supercluster unit. My group has built multiple supercomputer
clusters at UTHSCSA and integrated them in the Texas Internet Grid for
Research and Education (TIGRE) via grid middleware based on the Globus
software stack. These resources have been developed to support our
demanding computationally intensive modeling applications.
- Software Development I am the project leader for the UltraScan
software development effort which uses modern open source tools to
create a high-performance data analysis package for the management of
research data from biophysical experiments. The software can be used
to simulate and design experiments, analyze equilibrium and velocity
sedimentation experiments, and includes a Laboratory Information
Management System (LIMS) with a MySQL database back-end. My expertise
includes programming in C, C++, MPI, PTHREADS, SQL, FORTRAN, PHP, HTML,
and other languages. Developments include portals and web interfaces to
supercomputing applications, queuing systems, remote execution calls,
XML procedures, and parallel file system storage technology. All methods
developed are usually wrapped in a user-friendly graphical user interface
(GUI) that follows standard programming procedures and provides intuitive
use to non-experts and experts alike. All GUI development is based on QT,
QWT and QWT3D, as well as libraries developed within my group.
- Experimental Design and Analysis: My laboratory engages in a
wide range of research projects involving proteins, protein assemblies,
DNA, DNA binding protein complexes, nano particles, nano- and carbon
tubes, colloids, interfaces, membrane proteins and other macromolecular
systems. I design and conduct experiments to test scientific hypotheses
and to research macromolecular structure and function, to characterize
shape, and size distributions. To this end I engage in frequent
collaborations with investigators at our institution and institutions
across the US, Canada, Asia and Europe. I use the software and methodology
developed in my laboratory to evaluate a large range of different systems,
which also serves my goal for evaluating the validity and generality of
the UltraScan software. My expertise in this field is unique and results
in important collaborative discoveries in biomedical sciences.