UC San Diego

In biology, signal transduction is the process by which an extracellular signaling molecule activates a membrane receptor that in turn alters intracellular molecules creating a response. The chemical signal binds to the outer portion of the receptors, which span the cell membrane with part outside the cell, changing its shape and conveying another signal inside the cell. Some chemical messengers can pass through the cell membrane, and bind directly to receptors in the cytoplasm or nucleus. Sometimes there is a cascade of signals within the cell. With each step of the cascade, the signal can be implied, so a small signal can result in a large response. Eventually, the signal creates a change in the cell, either in the expression of genes in the nucleus or in the activity of enzymes in the cytoplasm. Since signal transduction and information measurement are so important for the cell, we are aiming to theoretically understand how signals are transferred inside cell and how cell measures its environment information. The first part of this dissertation focused on the compartmentalization of second messengers. Intracellular signal transduction is largely carried out by second messenger molecules. It is well known that a variety of signaling pathways can share a common second messenger, generated through different external stimuli. Obviously, this leads to the potential of cross-talk between these pathways. One possibility to avoid this cross-talk and thus ensure pathway specificity is to create spatial regions in which the concentration of the second messenger is markedly different. By spatially localizing the targets of the second messenger in these microdomains it would be possible to excite different pathways for different external stimuli. The second part of this dissertation studied how cell as a information processing machine senses chemical gradients in its environment. Using information theory, a formula for the mutual information between the input gradient and the spatial distribution of bound receptors was derived. By estimation theoretic methods, the physical limits of gradient sensing was also determined for both circular and ellipse cells. The third part of this dissertation investigated how biological processes are controlled by biochemical switches which are regulated by upstream signal, in order to understand how input fluctuation affect the dynamic of a molecular switch. This understanding is critical toward a full understanding of noise regulation in biological signaling systems