Science in Sarkar Lab
Innate immunity of an organism is the inborn protection against invading pathogens. Because it is inborn, and entrusted with the protection of host from a vast array of previously unknown invaders, the innate immune system generates a generalized alert response upon pathogen detection. This alert is chemically mediated by a class of molecules called Cytokines. A critical task for this host protection system is to distinguish foreign or non-self, from self, and initiate their destruction or containment. The sensors or the receptors of the innate immune system accomplish this by recognizing specific molecular patterns, which are common to pathogens or pathogen associated molecules, but absent in the host. We focus on a particular subset of these sensors/receptors, which are involved in sensing virus infection.
In order to protect the host from viral invasion, the innate immune system has evolved sensors to detect the viral nucleic acids. Several unique features of virally produced DNA or RNA are exploited to distinguish viral nucleic acids from that of the host.
One such unique nucleic acid is double-stranded RNA (dsRNA) – a common byproduct or intermediate in viral genome replication. In mammals, receptors like Toll-like Receptor 3 (TLR3), Retinoic acid-Inducible Gene I (RIG-I) and Melanoma Differentiation-Associated gene-5 (MDA5) are the three known sensors of dsRNA.
Single-stranded viral RNA is sensed by Toll-like Receptor 7 and 8 (TLR7 and TLR8), while viral DNA is detected by Toll-like Receptor 9 (TLR9), and other less well characterized receptors.
We study four related aspects of innate immunity:
- Screening - The signaling process involved in cytokine production after virus infection.
- Signaling - Develop modulators for these signaling pathways.
- Virus - How virus evade host innate immune response.
- Cancer - The contribution of innate immune response in cancer.
Further Reading
For More Information on Innate Immune receptors and their involvement in several diseases please see
Immunity's Early-Warning System by Luke A. J. O'Neill, Scientific American, Jan 2005. (PDF)
A Revival For Immunity; Biotech Looks Anew at Old Ideas On Using the Body's Own Defenses by Andrew Pollack, New York Times, Oct 5, 2005. (PDF)
Recognition of microorganisms and activation of the immune response by Ruslan Medzhitov, Nature, Oct 18, 2007. (PDF)
Wikipedia entries on "Innate immune system" and "Toll-like Receptors" are quite comprehensive.