Applications from suitably qualified individuals are invited for a Doctorate (PhD) degree position at the South African National Bioinformatics Institute at the University of the Western Cape in Cape Town.
Bioinformatics is a specialist discipline straddling the fields of biology, mathematics and computer science and is integral to modern biological research. The South African National Bioinformatics Institute (SANBI) is situated at the University of the Western Cape (UWC) in Cape Town. Our primary focus is the development and implementation of computational methodologies that allow researchers to accelerate their genomics data analyses.
This PhD degree project will be jointly funded by the South African Medical Research Council (SAMRC) and National Institutes of Health (NIH), USA and represents an opportunity to be part of an exciting international HIV research team characterizing the dynamics of the latent viral reservoir and determinants thereof in African populations. This reservoir exists during treated infection and represents the greatest barrier to a cure for HIV. The proposed work has potential to make important contributions to HIV reservoir research in Sub-Saharan Africa.
Project Description: Exploring the role of the viral long terminal repeat (LTR) in HIV-1 latent reservoir dynamics
Strategies to cure HIV are aimed at either complete clearance of the latent reservoir or a state of remission (or functional cure) in which viral replication is controlled in the absence of treatment. The latter is a much more attainable goal and requires an understanding of viral targets to reduce/restrict reservoir size or further silence the reservoir. As the HIV LTR regulates viral transcription and a number of studies now report its role in HIV latency, it is a potential target for such strategies. Currently, there are no data reporting on the evolution of this viral promoter element over time and little is known about the genetic or structural determinants of its role in latency. Next-generation sequencing technologies allow for an in-depth look at viral variants and tracking of viral evolution over time. To our knowledge, this method has not been applied to study LTR evolution. Furthermore, in vitro models exist that allow investigation of LTR function including LTRs of different genotypes. Such technologies need to be exploited to further uncover the role of the viral LTR in HIV latency.
The primary aim of the PhD project will to characterize intra-participant LTR evolution in a group of South African women living with HIV and the role of LTR genotype in latent reservoir dynamics.
This will include multiple objectives that may change as the project develops. These may include: 1) performing data mining of online and local repositories for longitudinal HIV-1 LTR sequence data; 2) designing and optimizing an Illumina MiSeq method for amplification and sequencing of the HIV-1 subtype C LTR in order to sequence the LTRs of HIV-infected individuals over pre-treatment infection; 3) evaluating the rate of evolution in the LTR and identify sites evolving under selection within longitudinal datasets; and 4) measuring LTR ‘latency potential’ of viruses from HIV-infected individuals sampled at acute and chronic phases of infection as well as from the long-lived latent reservoir using an established in vitro latency model.
Requirements for an PhD:
● A MSc in Biological Sciences, Statistics, Mathematics or Computer Science
● Proven experience in the analyses of molecular sequence data
● Demonstrable experience of working in a wet lab including expertise in nucleic acid extraction, PCR, agarose gel electrophoresis, and cell culture
● Experience in flow cytometry and next-generation sequencing is an advantage
● Experience in working with infectious material is an advantage
● Experience in the use of R or Python programming languages is an advantage
● Experience in the use of phylogenetic methods is an advantage
● Have a basic understanding of viral evolution
● Ability to work independently as well as in a team
● Ability to critically analyze and summarize data
● A South African driver’s license is an advantage
General conditions and application procedure:
The PhD position is offered as a three-year bursary, subject to attainment of agreed annual performance targets and available funding. The student will mostly be based at the University of Western Cape or the University of Cape Town, depending on project requirements.
Candidates should be available to start on or before the 1st February 2023.
Applicants should submit a detailed CV, the names and contact details of three references, a copy of their SA ID document or passport, university transcripts and other qualifications, theses and publications along with a covering letter summarizing the reason for applying and motivating why they are suitably qualified to take up the position(s), to Dr. Gordon Harkins (gordon@sanbi.ac.za) and Dr. Melissa-Rose Abrahams (melissa-rose.abrahams@uct.ac.za).
Closing date:
Applications must be submitted by no later than Tuesday 31st December 2022.
SANBI is committed to employment equity and redress, and these positions are subject to the conditions of the South African Medical Research Council (MRC). There is preference for South African citizens or South African permanent residents, and individuals from previously disadvantaged backgrounds. SANBI reserves the right not to make an appointment to the position as advertised. Only short-listed applicants will be contacted.