Kirby Institute Seminar Series presents

		Ms Rosemary A. Aogo PhD Candidate, Infection Analytics Program, Kirby Institute, UNSW Sydney Rosemary Aogo is an Applied Mathematician with Masters degrees in both Mathematical Sciences and Biomathematics (Stellenbosch University, South Africa). Her current PhD work involves using experimental data, mathematical and statistical models to understand drug action and host responses during malaria infection. Her research interests include applying mathematical tools to understand biological systems, and most importantly, the biology of infections.
		Mrs Lianne Lansink PhD Candidate, QIMR Berghofer Medical Research Institute/Queensland University of Technology (QUT) Lianne Lansink is a second year PhD Candidate. She acquired her BSc from the University of Amsterdam, during which she spent 9 months at QIMR Berghofer initiating her current project in collaboration with the Infection Analytics Program at the Kirby Institute. She has always been intrigued by tropical infectious diseases, in particular malaria.

Abstracts

Mathematical modelling to understand antimalarial drug action and host immune responses in malaria
Ms Rosemary Aogo

Malaria still remains a global health problem and is responsible for approximately half a million deaths every year. Successful immunological and drug interventions are urgently needed to better control infection. In this talk, I will present some of the key findings of my thesis, where I investigate the mechanisms of action of existing and novel antimalarial drugs and host immune responses in controlling infection.

The effect of host inflammation on malaria parasite growth in vivo
Mrs Lianne Lansink

It has become increasingly apparent that asexual intra-erythrocytic Plasmodium parasites can sense and respond to environmental changes in the mammalian host, for example, in nutrient availability. We previously reported host-mediated slowing of the intra-erythrocytic developmental cycle (IDC) during P. berghei ANKA infection in mice. Here, we hypothesized that host pro-inflammatory responses themselves could induce impaired maturation.

Consistent with this, systemic treatment of mice with LPS, but not CpG or Poly I:C, triggered impaired in vivo maturation of parasites, which correlated with plasma TNF/IFNγ levels. In vitro culturing experiments suggested the presence of an inhibitory factor in plasma from LPS-treated, or acutely-infected mice. To study responses to host inflammation by heterogeneous, asynchronous, populations of Plasmodium parasites, we constructed a Plasmodium single-cell RNA-seq reference atlas in rag1-/- mice that lack pro-inflammatory responses. Lineage tracing reconstructed a circular progression from early to mature stages, and suggested greater transcriptomic plasticity in ring stages than in schizonts. Ongoing scRNAseq studies will compare the transcriptomic responses of parasites in the presence or absence of a host inflammatory response.