Influenza viruses cause hundreds of thousands of deaths each year. Despite a long-standing awareness of 'flu' in the research community, leading to the availability of vaccines for almost 70 years, it still presents a very real concern for public health. This is largely due to the fact that influenza viruses undergo a process known as antigenic drift. This allows the virus to sidestep immune responses that have been formed in individuals who have been exposed to the virus in the past or who have been vaccinated against influenza, by acquiring mutations in the surface protein haemagglutinin. By using electron microscopy to solve the structure of many haemagglutinin molecules from diverse strains of influenza and leveraging protein structure data from previous studies, we plan to construct computer models of the changes in this key protein which allow it to evade immune responses. These models will help vaccine designers and public health officials to anticipate trends in the spread of different flu strains and prevent deaths from flu by designing more effective vaccines faster.
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Toxoplasma gondii is a parasite which causes the disease toxoplasmosis. This usually does not cause serious symptoms but can be extremely dangerous for immunocompromised people or when contracted during pregnancy. The mitochondrial electron transport chain (mETC) is essential for survival of T. gondii. The mETC is composed of multiple large membrane-bound complexes, labelled from complex I to complex IV, which generates adenosine triphosphate (ATP), the energy currency of the cell. The clinical drug atovaquone targets the mETC, showing the mETC is a viable drug target. My project will focus on complex II. Previous research on T. gondii complex II has revealed it to be much larger and contain more subunits than complex II from other organisms such as mammals or bacteria. My aim will be to optimize purification of T. gondii complex II and solve its structure using cryo-electron microscopy. This will allow me to understand the mechanism of the complex further. Researching complex II will further the biological understanding of the parasite Toxoplasma gondii as well as contributing to the mitochondrial biology field by looking at this evolutionary diverse species. Having a structure would aid in further research, such as drug development against the parasite.
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