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   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.

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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.