Dr Alex Sigal is member of Faculty at the Africa Health Research Institute and a Research Group Leader at the Max Planck Institute for Infection Biology in Berlin, Germany. Alex’s core research direction is investigating reservoir mechanisms in HIV and TB, including the switch between quiescence and active infection in TB, and in the cellular source of the reservoir in HIV. His lab at AHRI works on reservoirs of infection in HIV and TB via experiments in the lab, computational approaches, and samples from cohorts of infected individuals uniquely available at AHRI. Find out more about the Sigal Lab here.
Click here for a full list of publications.
The aim of Dr Alex Sigal’s research group is to understand HIV and TB transmission between cells and how it affects the persistence of infection, sensitivity to drugs, rate of the infection cycle and, for HIV, the formation of a quasispecies. An infection where successful transmission occurs between cells has to be targeted differently from infection where the pathogen persists by quiescence or latency. Such transmission occurs in the presence of drug or immunological control if multiple pathogens pass between the infected donor and uninfected target cell, making it more difficult to inhibit every pathogen transmitted. Multiple transmissions occur in HIV by cell-to-cell spread and in TB by the internalisation of multi-bacterial clumps. In HIV, multiple infections per cell also have consequences for evolution, as it reduces the selective pressure at low antiretroviral drug concentrations, allows replication at higher drug concentrations, and enables co-infecting viruses to share components in a process known as complementation. The lab is studying how these effects shift evolution trajectories and lead to therapy failure, and where in the body they occur. To study transmission and evolution, the Sigal Group uses in vitro culture, where they 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. The group combines their experimental results with computational modelling, and use samples from human donors to test the clinical relevance of the results obtained in the lab.
Meet the Team
Gila Lustig obtained her PhD from the Weizmann Institute of Science on the role of phospholipase D in cancer cell signalling and did her postdoc with Patricia Johnson at UCLA on the factors involved in the pathogenesis of Trichomonas vaginalis. Gila is interested in understanding the role of cell-to-cell spread of HIV in creating a reservoir of infection and the possible interactions with other STIs in HIV transmission.
Laurelle completed her Honours and Masters degrees in Biochemistry at the University of KwaZulu-Natal (UKZN) and did her research on vaccine strategies for trypanosomosis. Laurelle is interested in what determines the patterns of HIV evolution to drugs and neutralising antibodies.
Shi-Hsia Hwa did her undergraduate degree at Lawrence University in Wisconsin, and Masters at the University of Wisconsin at Madison. She then worked at Inviragen/Takeda Vaccines. Shi-Hsia Hwa is interested in the role of antibodies in modulating TB infection.
Ana Moyano de las Muelas
Ana Moyano de las Muelas has a degree in Biology from Universidad Autónoma de Madrid, and a Masters in Microbiology from the Universidad de Alcalá. Her Masters research focused on viral determinants of HIV progression. Ana joined the Sigal Lab in 2016 as a research intern. She is now doing her PhD focusing on finding the cellular determinants of HIV progression.
Jessica Hunter completed her Honours in Medical Microbiology through UKZN in 2014. During the second half of 2014 she also worked as an intern in the Sigal Lab. Jessica is currently pursuing her Master’s degree under the supervision of Dr Alex Sigal. Her Master’s project investigates the number of proviral integrations per cell in cell-to-cell spread of HIV.
Isabella Ferreira completed her undergraduate at the University of Cape Town and her Honours in Genetics at the University of KwaZulu-Natal. Her Master’s project is investigating the cellular HIV reservoir in lymph nodes, which is thought to be critical for HIV replication and persistence in antiretroviral treatment suppressed individuals.
Hylton completed his undergraduate and honours degree at the University of KwaZulu-Natal, showing interest in the regulatory genetic processes that govern early eye development. He is currently focussed on understanding the role that host cell death plays during a tuberculosis infection.
Sandile Cele holds a Masters degree in Biochemistry from UKZN. He previously worked as a research scientist intern at the Technology Innovation Agency, Institute for Diagnostic Research. Sandile's key responsibilities at AHRI include the maintenance and upkeep of BSL3 and BSL2 laboratories, processing and storage of human samples, performance of lab experiments pertaining to immunology and molecular biology, as well as the development of SOPs.
Yashica Ganga holds a Masters degree in Medical Science (Physiology) from UKZN. Her work is in the field of HIV and HIV Associated Neurocognitive Diseases, namely HIV Associated Dementia. She is currently working on drug sensitivity in HIV cell-to-cell spread in primary cell lines. Her other duties include processing and storage of clinical samples, administrative duties, general lab duties and routine BSL3 and BSL2 maintenance and upkeep.
Selected Recent Publications
Mahamed, D., Boulle, M., Ganga, Y., Mc Arthur, C., Skroch, S., Oom, L., Catinas, O., Pillay, K., Naicker, M., Rampersad, S., Mathonsi, C., Hunter, J., Sreejit, G., Pym, A. S., Lustig, G., & Sigal, A. (2017). Intracellular growth of Mycobacterium tuberculosis after macrophage cell death leads to serial killing of host cells. eLife, 6, e22028. doi: 10.7554/eLife.22028.
Boullé, M., Müller, T. G., Dähling, S., Ganga, Y., Jackson, L., Mahamed, D., Oom, L., Lustig, G., Neher, R. A., & Sigal, A. (2016). HIV Cell-to-Cell Spread Results in Earlier Onset of Viral Gene Expression by Multiple Infections per Cell. PLoS Pathog, 12(11), e1005964.
Sigal, A., & Baltimore, D. (2012). As good as it gets? The problem of HIV persistence despite antiretroviral drugs. Cell host & microbe, 12(2), 132-138.
Sigal, A., Kim, J. T., Balazs, A. B., Dekel, E., Mayo, A., Milo, R., & Baltimore, D. (2011). Cell-to-cell spread of HIV permits ongoing replication despite antiretroviral therapy. Nature, 477(7362), 95-98.
Sigal, A., Milo, R., Cohen, A., Geva-Zatorsky, N., Klein, Y., Liron, Y., Rosenfeld, N., Danon, T., Perzov, N., & Alon, U. (2006). Variability and memory of protein levels in human cells. Nature, 444(7119), 643-646.