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Open Positions

We are looking for motivated and enthusiastic researchers at the Masters, PhD, or postdoctoral level, to join the lab in the brand new K-RITH research center in Durban, South Africa.

Systems Infection Biology

Alex Sigal completed his PhD at the Weizmann Institute of Science in the field of Systems Biology, where he investigated the dynamics of cell-to-cell differences using a novel library of endogenously tagged proteins. He went on to postdoctoral training at the California Institute of Technology, where he focused on understanding the mechanisms of persistence in HIV, and specifically how directed spread of the virus by cell-to-cell contact can lead to reduced sensitivity to infection inhibitors. He joined the Kwazulu-Natal Research Institute for Tuberculosis and HIV (K-RITH) in Durban, South Africa as an Assistant Investigator in 2012 and concurrently became a Junior Research Group Leader at the Max Planck Institute for Infection Biology.

Research interests

A fundamental question in pathogenesis is what makes some diseases chronic. The disease agent, which may be a virus, bacterium or parasite, is cleared very slowly, and in some diseases never cleared, by the immune system or therapy. The reasons in the case of HIV and TB can be broken down into latency (HIV) or dormancy (TB), incomplete drug or immune effector penetration and function, and modes of spread that make infection very probable despite inhibition by cellular or pharmacologic agents.

The goal of our laboratory is to better understand reservoir formation in HIV and TB infection, and specifically what interactions in the cellular milieu of the infection microenvironment make infection insensitive to inhibition by the immune system or therapy. Furthermore, we will focus on understanding the dynamics and constraints of one mechanism whereby the reservoir can re-seed more generalized infection in the presence of therapy, which is the evolution of drug resistance.

To study HIV reservoirs and evolution we will continue to use in vitro culture where we have the ability to control the system and add or remove layers of complexity and thereby define the important components that affect the degree of inhibitor insensitivity and the rate and trajectory of the evolution of genetic resistance. In TB, we will investigate the contribution of non-genetic cell-to-cell variability to the persister phenotype, as well as T cell specificities that may enable the sequestration of the disease in a reservoir for life.

Perspective

The long-term goal of our research is

  1. Define key cellular players in persistence of HIV and TB
  2. Understand evolutionary trajectories as a function of inhibitor concentration, genetic makeup of the pathogen population, and microenvironment
  3. Study the persistence of TB due to cell-to-cell variability in the bacterial population, and
  4. Study the elements of a successful immune response to TB that prevent it from exiting the reservoir and causing active disease
 
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