Barts and The London School of Medicine and Dentistry at Queen Mary University of London and A*STAR PhD Studentship: Tracking age-related changes in HBV-immunity at the single cell level
Chronic Hepatitis B (CHB) is the leading global cause of hepatocellular cancer (HCC). The early phase of CHB designated as “immune tolerant” (IT) phase was considered a benign disease state, devoid of disease progression. Our recent work using novel experimental approaches re-examined the concept of immune tolerance from an immunological and molecular perspective. Similar to patients with biochemical activity labelled immune active (IA) who are considered for treatment, we demonstrated a similar disease pattern in IT patients. We showed that they had evidence of HBV-specific immunity, HBV DNA integration; a surrogate marker for host DNA damage and clonal hepatocyte expansion; a risk factor for HCC indicating that earlier therapeutic intervention may be required in this group of younger patients. To further explore this exciting and important area in HBV translational research we will augment our collaborative efforts (PK, AB, JC) with the co-supervision of a joint-PhD student. This project will involve the deeper phenotyping of immune cells in HBV. From carefully characterised cohorts of HBV patients at Barts Health, across the disease phases and age spectrum, blood and tissue samples will be used to extract DNA/RNA to undertake deep sequencing of the virus along with the T cell receptor (TCR) repertoire. In addition, single-cell RNA-sequencing analysis of the samples will be undertaken to identify gene signatures associated with immune control/progression of HBV, which will be correlated at the protein level. These data will be used to identify molecular interactomes within tightly correlated gene clusters, representing functional gene networks/biological pathways. The bioinformatic analysis of these networks will offer novel molecular/immune insights into the correlates of disease and new hypotheses for age-related pathogenic mechanisms. These data will be interrogated with clinical parameters to better stratify patients. Multiple clinical trials of novel agents for HBV cure are currently being tested. Both PK and AB are collaborating with industrial partners to better stratify disease to develop individualised HBV therapies. This will provide a springboard to link the data generated through this collaboration with industry. The PhD student will be supervised by PK and Dr Upkar Gill (CL at QMUL) and JC, AB and Dr Le Bert (Senior Research Associate). They will learn state-of-the-art laboratory techniques, data analysis and interpretation with an extensive focus on bioinformatics and single-cell work. The partnership with industry will be highly advantageous for students offering the potential to explore opportunities in Pharma and facilitate access to these schemes, ultimately leading to improved career prospects at a post-graduate level.
We are seeking highly motivated candidates to pursue their doctoral studies with this project. The eligibility criteria for candidates are:
• Obtained a first/upper second-class honours degree (or equivalent from a non-UK university) in a relevant biomedical or life sciences subject.
• A masters level degree in a similar discipline is desirable and will be looked upon favourably, although not essential.
• Research experience in a laboratory based setting, as part of, or outside of, an undergraduate or masters degree course is essential.
• Experience in immunological techniques including flow-cytometry, ELISA, cell culture and anlaysis is highly desirable along with an idea of molecular biology methods such a PCR, DNA & RNA extraction.
• A good knowledge of English and ability to express themselves clearly in both speech and writing.
• Strongly motivated for doctoral studies, must have demonstrated the ability to work independently and to perform critical analysis
A*STAR Research Attachment Programme (ARAP): This PhD programme is a collaboration between A*STAR and Queen Mary University of London (QMUL) to provide research opportunities for PhD students at A*STAR Research Institutes. Under this programme, PhD students from overseas universities will spend two years at A*STAR Research Institutes under the joint supervision of staff of the A*STAR Research Institutes and QMUL.
The primary supervisor is Professor Patrick Kennedy: https://www.qmul.ac.uk/blizard/staff/centre-for-immunobiology/staff/patrick-kennedy.html
The co-supervisors in Singapore are Dr Jinmiao Chen: https://www.a-star.edu.sg/sign/PEOPLE/Joint-Adjunct-Investigators/Investigator-Details?givenName=Jinmiao&lastName=CHEN
and Professor Antonio Bertoletti: https://www.a-star.edu.sg/sics/About-Us/Our-Investigators/Antonio-Bertoletti
Interviews are expected to take place in April
Starting date: September 2019 (dates can be flexible)