Applications from suitably qualified individuals are invited for two Masters in Science (MSc) degree positions 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.
These MSc degree projects are jointly funded by the Medical Research Council of South Africa and National Institutes of Health (NIH), USA and represent 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 one: Timing of entry of HIV-1 variants into the latent reservoir using Bayesian analyses
The stability of the latent HIV-1 reservoir necessitates life-long treatment as decay is projected to take >70 years to clear HIV infection if treatment is initiated in chronic infection. The majority of HIV-infected individuals in Sub-Saharan Africa initiate ART in chronic infection. Therefore, understanding the key determinants of reservoir establishment, size and maintenance is imperative to designing appropriate HIV cure interventions. The successful applicant will make use of longitudinal next-generation sequence data from a population of subtype C infected women from the CAPRISA 002 cohort to elucidate viral evolution patterns and generate a pre-treatment evolutionary timeline with which to date viruses isolated from the long-lived latent reservoir. This will involve the analysis of genomic sequences using a genealogy based population genetics approach in a Bayesian fully probabilistic inference framework in BEAST v1.10. These analyses will aid in better understanding the establishment of viral reservoirs in individuals who initiate therapy. The proposed work will contribute to a larger study investigating reservoir dynamics that will also include measurement of reservoir size (as determined by a newly reported highly accurate reservoir sizing method developed using American populations), viral promoter function and nef gene function.
Project two: Investigation of the viral dynamics involved in HIV-1 subtype C latent reservoir formation and evolution
HIV evolution pre-ART leads to a virological history of the natural infection within an infected individual represented by multiple variants that arise and expand over time. It is known that the HIV latent reservoir is established during acute infection and that variants from both early infection time points as well as time points proximal to ART initiation can be identified in the cellular long-lived reservoir. However, it is unknown if different distinct compartments in the body contribute to the latent reservoir in different ways and to what extent the reservoir contributes to viral evolution during viremia by reseeding of infection. The successful applicant will optimise an Illumina MiSeq protocol for the sequencing of approx. 500 base pair HIV-1 genome regions from cervico-vaginal lavage (CVL) samples. Thereafter the candidate will make use of these and existing next-generation sequence data from plasma to elucidate the contribution of viral variants from samples collected from the blood and cervix to the long-lived latent reservoir in a longitudinal sample of subtype C infected women from the CAPRISA 002 cohort. The successful applicant will analyse for each participant data set, longitudinally sampled matched CVL, plasma, and viral outgrowth sequences under a range of different evolutionary models using BEAST v1.10. These analyses will provide estimates of the timing of the establishment of the reservoir and the most probable source along with the dates, magnitude, and direction of the independent movements between the different tissue compartments within each individual over the course of infection. From these estimates we will be able to determine the proportion of the reservoir that is established by either compartment, and conversely, how the reservoir contributes to the longitudinal evolutionary patterns in the blood and the cervix.
Requirements for an MSc:
● A BSc (Hons) or equivalent in Biological Sciences, Statistics, Mathematics or Computer Science
● Competent in the analyses of molecular sequence data
● Experience in the use of R or Python programming languages is an advantage
● Experience in the use of Bayesian phylogenetic analyses methods is an advantage
● Experience with wet lab work including PCR and agarose gel electrophoresis
● Have a basic understanding of viral evolution
● Ability to work independently as well as in a team
● Ability to critically analyze and summarize data
● Computer literacy, and experience with Office software (Excel, Word, Power Point)
● A South African drivers license is an advantage
General conditions and application procedure:
The MSc positions are offered as a fixed two-year bursary contract, subject to attainment of agreed annual performance targets. Tax-free grants of R147, 000.00 per annum are available to the MSc students with the option of renewal for another year based on satisfactory performance. Students 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 2021.
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 and 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).
Candidates may indicate interest in more than one position, but should clearly indicate which positions they are applying for.
Closing date:
Applications must be submitted by no later than Monday 6th Jan 2021.
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.