Coordinator: Herbert Levine (UCSD)

    Cells utilize signaling networks to make many decisions based on input from the external world. One of these decisions concerns directed motility; especially during development both also as part of the normal dynamics of, for example, the immune system, cells employ surface receptors to measure chemical gradients and bias their motion accordingly. Unlike bacteria which act as point sensors and determine static gradients by temporal sampling, most evidence to date suggests that receptor occupancy differences across a static eukaryotic cell provides enough input for this sensing to take place.

    One system that has received a great deal of attention as a genetically-manipulable model of eukaryotic chemotaxis is the cAMP sensing of the cellular slime mold, Dictyostelium discoideum. Recent advances in subcellular-scale fluorescence microscopy have revealed that the first steps in the chemotactic response involve modification of the phospholipid membrane at the cell's leading edge. This modification leads to the recruitment of various proteins to the membrane, thereby initiating the overall process which culminates in the extension of a pseudopod in the direction of the chemical source. Similar findings have been reported for mammalian neutrophils. Various models have been put forth to explain these new data, but the mechanisms remain ill-understood. But, new experimental techniques (single molecule sensing, microfluidics based control of chemical stimuli, etc) just now coming on-line, together with continued work on these theoretical models should lead to rapid progress over the next few years.

Our goal in this mini-workshop is to bring together biologists (working both on Dictyostelium and on other cells) and modelers (from the physics and engineering communities) interested in eukaryotic chemotaxis. The interactions among the participants should be able to speed up progress in systems already under intense study, to enable new experiment/theory collaborations to take root, and finally, in light of the overall context of the ITP program, to help place this particular sensing system in the broader framework of molecular networks as a robust yet flexible solution to the signal processing needs of
the cell.

Preliminary schedule:
 

	Wed. 3/12	Thu 3/14	Fri 3/15
10:00am	W. Loomis (UCSD) The Dicteostelium motility cycle	H. Bourne (UCSF), A Neutrophil's Sense of Direction	W.-J. Rappel (UCSD) A temporal approach to modeling chemotactic signaling
11:00am	Break	Break	Break
11:30am	Dan Wu (U.Conn) Molecular basis of chemotactic signal transduction	A. Narang (U.Florida) Modeling Phospholipid Signaling Dynamics	E. Bodenschatz (Cornell) Towards a new generation of chemotaxis experiments
12:30pm	LUNCH	LUNCH	LUNCH
2:00pm	KITP Colloquium	R.Firtel (UCSD) Dicty chemotaxis visualized by subcellular fluorescent microscopy	H.Levine (UCSD) How close are we to understanding chemotactic response?
3:00pm	Tea/Cookies	Tea/Cookies	Tea/Cookies
3:30pm	P. Iglesias (Hopkins) Adaptation and Response in Dicty Chemotaxis	T.Meyer (Stanford) Eukariotic Signal Transduction Networks	Discussion
4:30pm	C-L Guo (Harvard) Yeast Chemotropism: Experiments and Models	Discussion
5:30pm	Wine&Beer	Dinner in SB