Dr Tony Holder

I have worked on parasitic protozoa for almost 40 years, first on Trypanosoma brucei but for most of the time focused on the malaria parasite. My initial studies were on glycosylation of the T. brucei variant surface glycoprotein and its now well-characterized glycosylphosphatidylinositol anchor. In malaria our early work showed that single proteins affinity purified from the parasite could be used to immunise against blood stage infection. One of these proteins is a member of the RH family that has recently seen resurgence in interest as vaccine candidates. The second is the well-known merozoite surface protein 1 (MSP1) which we characterised extensively. We have described a range of parasite proteins involved in invasion and colonisation of erythrocytes, particularly proteins located on the parasite surface and in apical secretory organelles. More recently we have contributed to understanding how the parasite's molecular motor provides the force that drives motility and invasion and the role of calcium dependent protein kinase 1 (CDPK1) in phosphorylating motor components. We have contributed to two potential drug discovery programmes based on our fundamental observations in parasite biology, and targeting CDPK1 and the enzyme N-myristoyl transferase (NMT). NMT-mediated acylation is a key modification of several proteins with roles in Apicomplexan biology such as the motor complex and the unique inner membrane complex structure that underlies the plasma membrane. Our work has ranged from molecular studies in the laboratory to community studies in human populations in malaria endemic areas. At the ‘molecular’ end of this spectrum this work covers genetic, protein structure and function, and cell biology studies.