Welcome to
the Gross Laboratory
'If
its moving, we're interested!'
Steven
Gross, Ph.D.
email: sgross@uci.edu
The big question my lab addresses is
that of protein
function: from the recent progress in molecular biology, we
either
know or will know the entire genomes of many organisms. Thus, we will
be
able to predict all of the proteins in those organisms. So, how
do
these
proteins function to achieve the desired biological activity?
Many
different tools are needed to adequately study this problem, so my lab
is extraordinarily cross-disciplinary, using biophysical as well as
genetic
and biochemical approaches. Of course, this problem cannot be studied
in
a vacuum--we need to ask and answer these questions in the context of a
specific biological process. We have chosen to study molecular
motors.
These motors are small enzymes that play
crucial
roles in many different cellular and developmental processes. Motors
such
as kinesin and dynein are required for mitosis and transport of many
sub-cellular
organelles such as mitochondria and endosomes, as well as
mRNA
localization
which is used to set up developmental axis. Motors also play a role in
many diseases: recent work shows that impaired transport can play a
direct
role in neuronal degenerative diseases such as Alzheimer’s,
and viruses
such as herpes (and probably HIV) hijack the motors to help them get
from
the cell’s periphery to the nucleus where they
replicate. Thus,
motors
are pretty important. How do we study them?
We use a variety of tools. The role of
the motor
proteins is to exert force, and “walk” along a
polymer track (such as a
microtubule or actin filament), dragging a cargo (e.g. a vesicle or
chromosome
or mRNA particle) with them. So, the functions we want to quantify, to
clarify these proteins activity are a) what is the force
that
the
motors can apply at a given time, and on a given cargo and b) how well
(i.e. how far and how fast) do
they move along the
polymer
track at a given time. From a biophysics perspective, we have developed
two sets of complementary techniques to quantify these functions. To
quantify
forces, we use an “optical tweezers”
(a “tractor beam”,
like
in the science-fiction show Star Trek) to stop individual moving
vesicles
and measure the forces that the motors moving them can exert. To
quantify
motion, we have developed particle tracking and analysis
software
that allows us to determine the position of the vesicle with a
resolution
of 8 nm, 30 times a second. So, we can accurately quantify the
important
aspects of motor function.
In addition, we work in Drosophila,
so we
can use genetics or biochemistry
to identify which
proteins
play a role in these processes. By making a mutation in a particular
protein,
and then using the biophysical tools to quantify how the motor
functions
were changed, we can better understand exactly what role that protein
has
in the overall process. Finally, by using biochemistry, we can
investigate
molecular interactions, to start to build a molecular picture of the
way
the motors are regulated. These more molecular models can then be
tested
by quantifying motion in a background with a more specifically
engineered
mutation, or by use of small peptides designed to block a particular
molecular
interaction. Thus, we integrate biophysics, biochemistry, and genetics
to better understand protein function in vivo and in vitro.
To try to learn general
rules, we study and compare the regulated motion of two
different
cargos: lipid
droplets moving in early embryos of the fruitfly Drosophila,
and pigment granules moving in a cultured cells
derived from
the
frog Xenopus laevis.
Information on The
Graduate Program and how to apply.
Students in
the Gross lab can
be enrolled
in a variety of programs of study. Dr. Gross is affiliated with the Center
for Biomedical Engineering, as well as the Physics
Department.
This web site is
always under
construction. 
