BNMC Seminar:  From molecular networks to multicellular structures:  predicting phenotype diversity and transitions

Anand R. Asthagiri
Assistant Professor of Chemical Engineering
Caltech

Multicellular patterns and structures emerge as cells execute instructions received from cues in their microenvironment.  Deciphering how cells integrate these cues to achieve an organized, functional structure is a fundamental question in biology with important biomedical implications in areas such as tissue engineering and regenerative medicine.  An essential element in multicellular assembly involves direct cell-cell interactions.  Cell-cell contacts are not only physical links between neighboring cells, but also sources of biochemical signals that instruct cellular behavior.  Our lab has been focused on elucidating how direct cell-cell interactions crosstalk with other environmental cues to affect individual cell fate choices, and thereby, generate multicellular patterns.

This talk will focus on our recent work in modeling multicellular patterning during the development of the organism, C. elegans.  An intriguing aspect of this system is that patterning is guided by both a soluble signal and direct cell-cell interactions.  Our computational analysis reveals that cell-cell coupling enhances cell perception of a gradient in the soluble signal [Giurumescu et. al. (2006) PNAS]. In addition, we have developed a parameter-unbiased, computational framework that accurately predicts wild-type and mutant phenotypes.  This ability to predict phenotypes has opened the door to intriguing new questions such as: what new phenotypes are possible, and what perturbations (mutations) render such phenotypes?  I will describe how answering these questions have offered a unique opportunity to explore both the molecular genetics of patterning and the evolutionary capacity of this signaling network for creating phenotypic diversity.