Doctoral fellow - Department of Internal Medicine and Pediatrics

Last application date Jan 31, 2022 00:00

Department GE35 - Department of Internal Medicine and Pediatrics

Contract Limited duration

Degree Msc. in bioscience engineering, biotechnology, biochemistry, (bio)medical sciences, pharmaceutical sciences, bioinformatics, computational biology, or related

Occupancy rate 100%

Vacancy type Research staff

About the HIV Cure Research Center:
The HIV Cure Research Centre (HCRC) headed by prof. Linos Vandekerckhove is nested in the department of Internal Medicine and Pediatrics at the Ghent University Hospital. The main focus of the research centre is to support and perform HIV reservoir and HIV cure related research. The HCRC has three important pillars. First, the group performs basic research into the establishment and maintenance of HIV reservoirs. Secondly, we fine tune and design new assays to monitor HIV reservoirs in patients and thirdly, we develop novel approaches to eradicate HIV reservoirs and design and perform clinical trials to further support the search for an HIV Cure.
Project description:
The major obstacle to reach an HIV-1 cure is the establishment of a persistent latent reservoir that is unaffected by current HIV-1 treatment. This reservoir has a varying impact on ongoing inflammation and immune activation in people living with HIV-1. Although the reservoir contains only a small fraction of replication-competent intact proviruses, these proviruses cause viral rebound upon therapy cessation, explaining the need for lifelong therapy. The underlying mechanisms that contribute to the establishment and maintenance of these reservoirs vary amongst people living with HIV-1 and are not completely understood.
Research Questions:
The viral reservoir size and activity varies amongst people living with HIV-1, resulting in several ‘extreme phenotypes’ ranging from people naturally controlling the virus without treatment to people that show a more rapid progression of the disease. Hence, understanding the drivers of these differences between these groups will give more insight in the establishment and maintenance of these reservoirs.
Therefore, we will address following questions:
1. How does the reservoir size and activity differ in a cohort of 2000 people living with HIV-1 and identify people with very high/low reservoirs and immune burden (extreme phenotype).
2. Which biological processes, patient characteristics and host correlates (omics) are associated with these extreme HIV-1 clinical phenotypes?
3. Search for host-dependent factors/correlates of reservoir size and activity by correlating several omics datasets (RNAseq, Cytokine profiling) to these reservoir measurements.
4. Evaluation of the full-length intact sequences and integration sites and link this to the integrated datasets.
Methodology:
Plasma samples and peripheral blood mononuclear cells isolated from whole blood are used to assess the HIV-1 reservoir size and activity in 2000 patients (as part of a Human Functional Genomics project, collected at Radboud UMC Nijmegen, Erasmus MC Rotterdam, OLVG Amsterdam and ETZ Tilburg). The HIV-1 reservoir is then quantified using digital PCR-based techniques that measure total/intact HIV-1 DNA and HIV-1 RNA transcripts. In addition, sequencing-based workflows are implemented to determine viral tropism and subtype. The plasma is used to conduct low-level HIV RNA assays or sequence circulating HIV RNA. At the end, all data is integrated with various omics datasets (e.g. cytokine profiles and transcriptome information) to identify host-dependent determinants, as performed previously on a limited patient cohort.

• You hold a master’s degree in bioscience engineering, biotechnology, biochemistry, (bio)medical sciences, pharmaceutical sciences, bioinformatics, computational biology, or related
• strong interest in HIV research with a drive to learn and adopt a variety of new techniques.
• hands-on experience in R or other programming languages is an asset
• experience with PCR-based techniques and sequencing is a plus
• You are a highly motivated and result-driven.
• You have strong problem-solving skills.
• You are a flexible team player with the capacity to work independently.
• You have good communication and writing skills (English).

For further information or to apply (include motivation letter and curriculum vitae with study results), please contact Prof. Dr. Linos Vandekerckhove ([email protected] ), Prof. Dr. Sarah Gerlo ([email protected] ) and Dr. Evy Blomme (in cc; [email protected] ).