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K-Rith

INVESTIGATOR

Alex Sigal

Alex Sigal was born in the former Soviet Union and grew up in Israel, the US and Canada. Moving around in childhood can elicit a flexible approach to living in different places and Dr Sigal believes that the researcher should go where he or she can do the best science. In the case of HIV and TB, he believes that place is South Africa, which on the one hand has first rate research infrastructure and on the other is the epicentre of these diseases. Dr Sigal was therefore excited to join K-RITH in collaboration with the Max Planck Society.

Sigal became interested in infectious disease during his MSc studies with Varda Rotter on p53 at the Weizmann Institute in Israel. At the time the Onyx-015 virus was being tested to selectively replicate and kill cancer cells based on their p53 status. This sparked Sigal’s interest in understanding what determines the outcome of interactions between the pathogen and the host cell. After finishing his MSc, Sigal travelled eastern Africa by bicycle, at times following truck routes. Along these he was able to see the changes brought about by the HIV epidemic. This trip left a strong impression. When he went back to do his PhD at Weizmann, Sigal looked for a unique perspective to view disease dynamics. He joined the laboratory of Uri Alon, a young scientist who was interested in finding rules in biological interactions, as part of the fledgling field of Systems Biology.

After completing his PhD, Sigal joined David Baltimore at the California Institute of Technology to study HIV. Here, his interests in infectious disease matured towards understanding why chronic infections such as HIV and TB cannot be cleared by the immune response and in the case of HIV, by current antiretroviral therapy regimens.

At K-RITH, Dr Sigal’s lab works 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 at K-RITH.

Dr Sigal is also a Max Planck Group Leader

Find out more about the Sigal Lab here

Get in touch with Alex Sigal via alex.sigal@ahri.org

ABOUT

Sigal Lab

Quantitative Infection Biology

The aim of the Sigal Lab 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. We are studying how these effects shift evolution trajectories and lead to therapy failure, and where in the body they occur.

To study transmission and evolution, we 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. We combine our experimental results with computational modelling, and use samples from human donors to test the clinical relevance of the results obtained in the lab.

Sigal Lab

Meet the Team

Deeqa Mahamed

POSTDOCTORAL RESEARCH FELLOW

Deeqa Mahamed was born and raised in Mogadishu, Somalia.  She received her PhD in Immunology and Infectious Diseases from Cornell University in 2012, studying Toxoplasma gondii virulence in Margaret Bynoe’s lab. Deeqa’s work in the Sigal lab focusses on elucidating the mechanisms of Mycobacterium tuberculosis pathogenesis, particularly with respect to drug resistance, persistence, and latency. Her research interests include reservoirs of infection, host-pathogen interactions and vaccine development.

Gila Lustig

RESEARCH ASSOCIATE

Gila 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.

Sanisha Rampersad

WORK EXPERIENCE INTERN

Sanisha is interested in understanding reservoirs of TB. She is currently doing her Honours degree at UKZN.

Kelly Pillay

WORK EXPERIENCE INTERN

Kelly Pillay holds a Bachelor of Biomedical Science degree, an Honours degree in Medical Microbiology and a Masters degree in Virology from the University of KwaZulu-Natal (UKZN). For her Masters research she investigated HIV-1 subtype C drug resistance. She is currently enrolled for a Bachelor of Medicine and Surgery degree at UKZN. Her love for science and desire to make a difference in the HIV and TB epidemics in South Africa led her to K-RITH. In the Sigal Lab, Kelly is currently working on image analysis of Mycobacterium tuberculosis infected cells identifying bacterium pick-ups, efferocytosis and cell death.

Ana Moyano de las Muelas

PHD SCHOLAR

Ana Moyano de las Muelas has a degree in Biology from Universidad Autónoma de Madrid, and a Masters in Microbiology – applied to public health and infectious diseases research – from the Universidad de Alcalá. Her Masters research focussed on viral determinants of HIV progression. Ana joined the Sigal Lab in early 2016 as a research intern, during which time she did a project to develop a stable cell line expressing VRC01 antibody. Her PhD project focusses on finding the cellular and viral determinants of virologic failure.

Yashica Ganga

RESEARCH LABORATORY TECHNOLOGIST 

Yashica Ganga was born and raised in Durban. She has a BSc in Medical Science (Physiology and Microbiology), an Honours degree in Medical Science (Physiology) and submitted her Masters dissertation in Medical Science (Physiology), at UKZN in mid-2015. Her work is in the field of HIV and HIV Associated Neurocognitive Diseases, namely HIV Associated Dementia. Yashica says it was always her dream to be a scientist and she is glad to be able to fulfill this at K-RITH. 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.

Steven Skroch

MASTERS STUDENT

Steven Skroch has a M.S. in Biomedical Engineering from the University of Wisconsin – Madison. He has an industry background in Quality Engineering for medical devices and aerospace. He also has significant experience in microfluidics, including involvement in two in-vitro diagnostic device startups. Steven is working on image analysis of cellular events, such as detection of phagocytosis and cell death. He is writing Matlab algorithms to correlate time-dependent behaviour in order to extract patterns and trends out of large data sets.

Shi-Hsia Hwa

PHD SCHOLAR

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.

Sandile Cele

RESEARCH LABORATORY TECHNOLOGIST

Sandile Cele has a BSc in Biomedical Sciences from the University of KwaZulu-Natal (UKZN), a BMedSc  Honours in Medical Microbiology from the Nelson R. Mandela School of Medicine and a Masters degree in Biochemistry from UKZN, Westville. Sandile previously worked as a research scientist intern at the Technology Innovation Agency, Institute for Diagnostic Research. Sandile’s key responsibilities at K-RITH as a Lab Technologist include the maintenance and upkeep of BSL3 and BSL2 laboratories, processing and storage of human samples, performance of laboratory experiments pertaining to immunology and molecular biology, maintenance of research documentation, recording of results and development of SOPs as well as administrative tasks and general lab responsibilities.

Oana Catinas

WORK EXPERIENCE INTERN

Oana is currently transitioning to microbiology as part of K-RITH’s SURF programme.

Laurelle Jackson

PHD SCHOLAR

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.

Jessica Hunter

MASTERS STUDENT

Jessica Hunter completed her BSc in Microbiology and Anatomy at the University of KwaZulu-Natal (UKZN) in 2013. She attended a mycobacteriophage genomics short course hosted by K-RITH in her third year of study and says it was this that really inspired her to pursue medical research. She 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 Masters degree under the supervision of Dr Alex Sigal. Her masters project investigates the number of proviral integrations per cell in cell-to-cell spread of HIV.

Colisile Mathonsi

WORK EXPERIENCE INTERN

Colisile Mathonsi holds a BSc degree in Biomedical Sciences, an Honours degree in Medical Sciences and a Masters in Medical Sciences. She was led to K-RITH through her desire to learn more about laboratory techniques and to expand her knowledge in the medical research field. Colisile is a work experience intern in the Sigal Lab at K-RITH, where she does microscopic image analysis using MATLAB. She is also involved with the Umkhumbane Schools Project in a mentorship role, helping school learners with career guidance as well as university and bursary applications.

Myshnee Naicker

WORK EXPERIENCE INTERN

Myshnee is interested in understanding reservoirs of TB. She did her Honours at UKZN and is currently doing her Masters in Microbiology.

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