- - Biolistic delivery and gene guns
- Kinetics and thermodynamics of protein folding
- Imaging of the development and behavior of C. elegans worms
- Imaging of primary and cultured leukocytes for HIV studies
- Microbial cultures in microchambers
- Chemotaxis, chemotropism, aerotaxis, thermotaxis and gradient response of cells and organisms
- Perfusion chambers to study the rolling, adhesion, and migration of blood cells and unicellular organisms
- Substrate rigidity sensing, traction force and TIRF microscopy of mammalian cells
- Oxygen level control and hypoxia on the cell and organism levels
UCSD Consortium Receives $5.5 Million to Study Cell Migration.
The National Institute of General Medical Sciences of the National Institutes of Health has awarded a five year, $5.5 million Program Project Grant to a UCSD consortium to study chemotaxis--the directed movement of cells up a chemical gradient--in the social amoeba Dictyostelium discoideum. Chemotaxis is a key component in a multitude of biological processes, including neuronal patterning, wound healing, embryogenesis and angiogenesis--the formation of blood vessels.
The overall aim of the project is to quantitatively study three distinct and sequential stages of chemotaxis using an approach that integrates novel experiments and mathematical modeling. These stages include the initial directional sensing process during which several key signaling components localize subcellularly, cell polarity which leads to clearly distinguishable fronts, backs and sides of a cell and motility which includes actual cell movement.
Experiments performed as part of the project will rely heavily on the use of microfluidic devices, which consist of tiny canals on a microchip. Microfluidic devices will provide precise control over the chemoattractant stimulus--the chemicals that attract cells. The goal of the research is to better understand chemotaxis of eukaryotic cells. Advances in this field will benefit diagnosis and treatment of medical problems involving cell migration.
The consortium consists of two theoretical physicists (Wouter-Jan Rappel, the PI of the grant, and Herbert Levine), two biologists (Richard A. Firtel and William F. Loomis) and Alex Groisman, a microfluidics expert in the physics department.
The grant also includes a subcontract to a microfluidics group at Cornell University (Carl Franck and Eberhard Bodenschatz).
- - Y. Gambin, V.Vandelinder, A.C.M. Ferreon, E.A. Lemke, A. Groisman, and A.A. Deniz,
"Visualizing a one-way protein encounter complex by ultrafast single-molecule
mixing", Nature Methods 8, (2011) PDF
- - P. Sundd, E. Gutierrez, M.K. Pospieszalska,
H. Zhang, A. Groisman, and K. Ley, "Quantitative dynamic footprinting microscopy reveals mechanisms of neutrophils
rolling", Nature Methods 7, 821-824, (2010) PDF
- - E. Lemke,
Y. Gambin, V. VanDelinder,
E.M. Brustad, H.-W. Liu,
P.G. Schultz, A. Groisman, and A. Deniz, "Microfluidic Device for
Single-Molecule Experiments with Enhanced Photostability", JACS, 131 13610–13612 (2009) PDF
- - M. Polinkovsky, E. Gutierrez, A.
Levchenko, and A. Groisman, "Fine temporal control of the medium
gas content and acidity and on-chip generation of series of oxygen
concentrations for cell cultures", Lab on a Chip 9, 1073-1084 (2009) PDF
- - H.J. Cho, H. Jönsson,
K. Campbell, P. Melke, J. W. Williams, B. Jedynak, A. M. Stevens, A. Groisman, and A.
Levchenko, "Self-Organization in High-Density Bacterial Colonies: Efficient
Crowd Control", PLoS Biology 5 (11), pp.
- - P. Herzmark, K. Campbell, F. Wang, K. Wong, H. El-Samad, A.
Groisman, and H. R. Bourne "Bound attractant at the leading vs. the
trailing edge determines chemotactic prowess" PNAS 104, pp. 13349-13354 (2007) PDF
- - S. Paliwal, P. Iglesias, K. Campbell, Z. Hilioti, A. Groisman, and A. Levchenko, "MAPK mediated bimodal
gene expression and adaptive gradient sensing in yeast" Nature 446 (7131), pp. 46-51 (2007) PDF
- - O. Shefi, C. Simonnet, M.W. Baker,
J. Glass, E. Macagno, and A. Groisman,
"Microtargeted gene silencing and ectopic expression in live embryos
using biolistic delivery with a pneumatic capillary gun", Journal of
Neuroscience 26, pp. 6119-6123 (2006) PDF
- - A. Groisman, C. Lobo, H. Cho, K. J. Campbell, Y. S. Dufour, A. M. Stevens and A. Levchenko, "A Microfluidic Chemostat for Experiments with bacterial and yeast cells", Nature Methods 2, pp. 685-689 (2005) PDF
- - C. Simonnet and A. Groisman, "Chaotic Mixing in a
Steady Flow in a Microchannel", Physical Review Letters 94, Art. No.
134501 (2005) PDF
- - A.
Groisman, and S. R. Quake, "A microfluidic rectifier: Anisotropic flow
resistance at low Reynolds numbers", Physical Review Letters, Art. No. 094501 (2004) PDF
- - A.
Groisman, M. Enzelberger and S.R. Quake,
"Microfluidic memory and control devices", Science 300, pp. 955-958
- - A.
Groisman and V. Steinberg, "Efficient mixing of liquids at low Reynolds
numbers using polymer additives", Nature 410, pp. 905-908 (2001). PDF
- - A.
Groisman and V. Steinberg, "Elastic turbulence in a polymer solution flow", Nature 405, pp. 53-55 (2000) PDF