Dr. Robert Striker is a faculty trainer in the CMB Program. Read the full research article at http://www.news.wisc.edu/13928

Striker Lab Research Interests

RNA viruses have high mutation rates and robust replication so they evolve rapidly to adapt to the exact cellular conditions of the host. Therefore RNA viruses are a challenge to the human immune system, as well as drug and vaccine development. We study the molecular details of what portions of the viruses are susceptible to evolutionary pressure.

When Hepatitis C Virus (HCV) infected patients require a liver transplant, the new liver also becomes infected and represents a unique “fast-action, real world camera” on evolutionary change in viruses. The input virus can be characterized, and monitored as it adapts to an immune system blocked by immunosuppressants, and a new liver. We have identified some of the genetic barriers the virus must overcome and how they are overcome in the lab.

One of the significant barriers we have identified is the cell cycle of the host cell. A bovine virus closely related to HCV grows in rapidly dividing cells in the gastrointestinal tract and the G1 phase, but other phases are much less permissive. We have adapted it to grow in slowly dividing, or cell cycle blocked cells that are more similar to the quiescent, nondividing liver cells that HCV thrives in. Early studies suggest that the ability of the virus to kill the host cells depends upon what stage of the cell cycle the host cell is in, and what stage of the host cycle the virus is adapted to.

The viral RNA polymerase is a source of mutational diversity and a target for drug design. We examine how naturally occurring and lab generated mutants in the polymerase affects fidelity, replication, and processivity. We have identified novel inhibitors of viral polymerases, and studying their mechanism and applicability to other RNA viruses (Flaviviruses, astroviruses and coronaviruses (SARS)).

http://www.medmicro.wisc.edu/department/faculty/striker.html