William Bishai’s research focuses on understanding how and why Mycobacterium tuberculosis, the bacteria that causes tuberculosis (TB), has been so successful at infecting humans. His laboratory uses genetic techniques to investigate how M. tuberculosis can slip under the radar of the human immune system. Bishai and his colleagues have learned that the microbe has developed a range of clever strategies to foil macrophages—immune system cells that attack and engulf invaders. Understanding the fundamental interactions that occur between the microbe and human cells is a critical step in developing new drugs or vaccines to treat tuberculosis, and Bishai plans to use the same strategy at K-RITH to develop new, quicker, and cheaper tools for diagnosing TB infection.
Adrie J.C. Steyn studies how Mycobacterium tuberculosis, the bug that causes tuberculosis, keeps itself alive in its host’s cells. Most people infected with TB don’t develop symptoms, a condition known as latent tuberculosis. In most people, latent tuberculosis never turns into active disease, and Steyn is interested in how the bacteria fend off attacks by the host’s immune system, particularly how the bacteria keeps from being destroyed.
Alasdair Leslie uses a technique called mass spectrometry to identify host cell proteins that undergo chemical changes immediately following infection. He focuses on proteins that undergo changes in phosphorylation, which can signal that a protein’s function has been switched on or off, in the first half hour following infection. At K-RITH, Leslie will also explore the effects of HIV and mTB infection in three-dimensional human tissue models. Under the right conditions it is possible to culture various types of human lung or gut cells in a Petri dish and coax them to organize themselves into structures that are virtually indistinguishable from the natural tissues. The models will be invaluable in studying how HIV severely damages the gut mucosa, a process that has been difficult to study in humans. Leslie is excited to bring these cutting-edge technologies to K-RITH.
Alex Sigal is interested in what makes some diseases chronic. The disease agent, which may be a virus, bacterium, parasite, or in some cases a cancer cell, is never fully cleared by the immune system or therapy. Instead it persists at low levels as an intra-patient reservoir which has the ability to re-seed widespread disease. In HIV, the reservoir is of critical importance since it persists in infected individuals despite the presence of suppressive antiretroviral therapy, and has so far been an insurmountable barrier to achieve a cure. Sigal wants to understand how reservoirs are created, and devise therapeutic strategies that specifically target reservoirs in human disease. At K-RITH, Sigal’s lab will be working on reservoirs of infection in HIV and TB both by experiments in the lab, computational approaches, and samples from cohorts of infected individuals uniquely available through K-RITH at Durban. He is looking for excellent candidates from any field of biology, and from physics, computer science, and engineering, to join him in discovery.
Alexander Pym has been investigating the genetic variation of Mycobacterium tuberculosis in KwaZulu-Natal, where the high prevalence of HIV infection is impacting transmission rates and is exerting selective pressure on the host's immune response. In collaboration with colleagues at the Nelson R. Mandela School of Medicine, he is working to connect these variations with the bacterium’s ability to infect humans and its ability to resist anti-TB drugs.
Frederick Balagaddé is interested in using microfluidics large scale integration (MLSI) to create low cost, sample-in-answer-out diagnostic tools and high throughput research platforms to address HIV and TB pathogenesis. At K-RITH, Dr. Balagaddé will establish a bioengineering research program that will leverage the power of microfluidics to multiply the output of clinical and laboratory technologists. Using specially designed microfluidic chips, technologists will be able to perform hundreds and thousands of diagnostics tests (or experimental measurements) simultaneously. Initial projects include: a high throughput HIV viral load measurement platform for monitoring antiretroviral therapy and chip-based platforms for investigating the pathogenesis of Mycobacterium tuberculosis and HIV. Click here to watch Dr. Balagaddé’s TED talk.
Jacques Grosset has worked for decades to test new drugs for tuberculosis in mice. He cites two main reasons for finding new tuberculosis drugs: to shorten treatment and to find ways to treat tuberculosis that is resistant to the available drugs. At K-RITH, he will continue his work with mice and his longstanding collaboration with Bishai. And given his extensive experience in running a clinical lab at a university hospital in Paris, Grosset will be in a position to mentor researchers looking to evaluate the effectiveness of TB drugs in patients.
ThumbiNdung'u is interested in understanding antiviral immune mechanisms and viral adaptation in HIV-1 subtype C infection as a pathway to vaccine development. The development of a safe, affordable and efficacious HIV-1 vaccine is perhaps the defining scientific challenge of our time. Rational vaccine design will require a better understanding of immune correlates of HIV-1 protection or control. My laboratory focuses on individuals who remain HIV negative despite possible repeated exposure to the virus and those infected who achieve durable viral control without the help of antiretroviral therapies. These individuals may hold the key to vaccine development or novel therapies.