ChEMS Seminar: Biological Switches and Modularity in Theory and Practice

 

 

 

 

Biological switches are biochemical subnetworks whose protein outputs can exist in two states, colloquially termed ON and OFF, depending on the inputs provided. These switches encode cellular decisions, which is why they are so ubiquitous in biological networks, and form an important component of gene regulatory networks. Since switches are such important control elements, it is no surprise that one of the first synthetic genetic networks constructed was a switch. My talk will consist of two stories about switches. In the first part of the talk, I will discuss our attempts, with collaborators, to build the first synthetic genetic toggle switch in a plant. Here the challenge was to develop a method of rapid quantitative testing of synthetic genetic parts for plants, so as to computationally predict switch properties. Mathematical modeling along with careful experiments helped us reach that goal, which helps bring plant synthetic biology for practical purposes within reach. In the second part of my talk I will discuss modularity of biological switches, using theoretical approaches. I will show that switches based both on positive as well as on negative feedback are quite sensitive to downstream connections. Under fairly plausible assumptions it is even possible to completely abrogate switch-like behavior just by incorporating protein outputs of the switch in downstream processes. This property begs the question: how can switches work robustly in nature in the face of this sensitivity? I will offer a few speculations in response.

 

Ashok Prasad is an Assistant Professor in the Department of Chemical and Biological Engineering at Colorado State University in Fort Collins. Ashok completed his PhD from Brandies University with Jane' (pronounced Yaney) Kondev in 2006. Ashok came to Brandeis as an older student than most. He had spent the previous 12 years teaching economics in an undergraduate college affiliated with Delhi University in India. Ashok has a Masters in Economics, however, in 2001 he came to Brandeis to complete a PhD in physics. While at Brandeis he fell in love with Biology, and after obtaining his PhD in soft matter physics, he completed a postdoc in computational immunology with Arup Chakraborty at MIT from 2006-08. He joined CSU in 2009.