Research Projects

Obtaining durable control of HIV is an urgent, unmet public health need. Elimination of HIV-infected cells will likely require potent function of HIV-specific CD8+ T cells. CD8+ T cell function is restricted in many people living with HIV (PLWH) by T cell exhaustion driven by an increased expression of immune checkpoints, such as programmed death-1 (PD-1). This exhaustion can be reversed by blocking the PD-1 immune checkpoint, and is conventionally achieved by anti-PD-1 monoclonal antibodies. A more scalable and affordable solution may be to downregulate PD1 expression using CRISPR-Cas13b. We have preliminary data in cell lines confirming we are able to knock down PD-1 – this honours project will continue this investigation by confirming knockdown in primary cells, and assessing the effect of CRISPR-Cas13b knockdown of PD-1 on T cell immune function in in vitro assays. If successful reversion of exhaustion is achieved with PD-1 knockdown we may also expand this project to knockdown of other immune checkpoint markers. During this project the student will learn the broadly applicable techniques of cell culture (including of primary cells) and spectral flow cytometry, as well as production of lipid nanoparticles.

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