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Systematic and quantitative characterization of viral-host interaction for rational therapeutic and vaccine designs


School of Biomedical Sciences

Applications accepted all year round Funded PhD Project (Students Worldwide)

About the Project

Systems biology is a field that is highly inter-disciplinary in nature, which involves molecular and cellular biology, genomics, structural biology, microfluidics, informatics and mathematic modelling. This integration and harmony in diversity indicates a generous openness towards innovative ideas and a holistic approach to answer fundamental questions in cell biology. Employing systems biology approaches, our lab aims at characterizing virus-host interactions and applying the insight with the use of high throughput platform to precisely design novel vaccines and therapies. Holding such mission, we have developed multiple high-throughput platforms, which enable us to define functional sequences in the entire viral genome at single nucleotide resolution, to identify viral-host protein complexes with low-abundance at whole proteome scale and to engineer proteins by in vitro evolution. (Du Y et al, Nature communication 2020) Equipped with these platforms, we would be able to serve both the scientific community and the general public with novel vaccine and therapeutic development. We are particularly interested in viruses that have immense impact on human society, such as SARS-CoV-2, influenza A virus, human immune-deficient virus (HIV) and Epstein-Barr Virus etc.

Project directions:
1. Viral engineer, Immunology and cancer immunotherapy. On the virus side, our lab has established a quantitative genetic profiling platform that systematically mutate every nucleotide on the viral genome. Unlike traditional genetics that focuses on the linkage between one mutation and one phenotype, genome-wide mutations under certain selection conditions such as interferons enable us to make precise engineering on viruses to specifically reduce potential pathogenesis and increase immunogenicity. (Du Y et al., Science 2018; Qi H et al., PNAS 2017) On the host side, we combined technologies on cellular and molecular biology, epigenetics, proteomic and mRNA-display to investigate host immune response in viral infection and vaccination (Du Y et al., Nature communication 2020). Meanwhile, we are developing cancer immune therapies using viruses deficient in immune-evasion functions to locally stimulate immune responses against tumor antigens. Furthermore, the engineered viruses we developed can be used as a tool to address a fundamental immunology question: how to fine tune adaptive immunity by modulating innate immunity.

2. Protein structure and engineer. Structure biology approaches allow us to understand protein-protein interactions at atomic resolution, whereas high-throughput genetics investigates functions at genomic scale. Combining these two provide us a powerful platform to understand the principles of protein-protein interactions. (Dai X et al., Nature 2017; Wu NC et al., eLife 2016; Olson CA et al., Current Biology 2014) In addition, we have integrated in vitro evolution, protein structure characterization and mass spectrometry technologies to engineer proteins. (Dai X et al., Nature 2017; Wu NC et al., eLife 2016; Olson CA et al., Current Biology 2014) Our goal is to use structure biology and protein engineer approaches to develop chemicals, peptides or proteins for disease diagnosis and therapies.

Supervisor
Professor Ren Sun obtained his PhD and got trained as postdoctoral and research scientist at the Department of Molecular Biophysics and Biochemistry, Yale University. He then joined the University of California, Los Angeles (UCLA) as an assistant, associate and then full professor. Prof. Sun was honored as Distinguished Professor at UCLA in 2018 and served as Associate Dean of David Geffen School of Medicine and Associate Vice Provost of UCLA from 2009 to 2019. He values bidirectional learning and spearheaded a reform to introduce interactive flipped learning for the graduate studies program back in UCLA. Prof. Sun is experienced in training postgraduates and has mentored 20 and 27 PhD and postdoctoral fellows over the years. Prof. Sun has recently moved his lab to the University of Hong Kong. Prof. Sun’s research interests span across virus-host interactions, genomics, single cell biology and, protein structure and engineering. He is one of the leaders using system biology, high-throughput genetics, multi-omics and nano-technology approaches to precisely define viral-host interactions.

Faculty information, funding opportunities and application deadlines: https://www.findaphd.com/phds/program/biomedical-research-hku-li-ka-shing-faculty-of-medicine/?i586p4119

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