The Trypanosome flagellar pocket -functions and adaptations in differentiation, pathogenicity and immune evasion. (360G-Wellcome-092201_Z_10_Z)

Cell body architecture of unicellular organisms influences a variety of cellular functions. The goal of this research is to understand how a specialised invagination of the trypanosome cell surface membrane called the flagellar pocket (FP) functions in differentiation, pathogenicity and immune evasion. I will investigate the stumpy form FP to determine what structures distinguish it from other lifecycle stages. I will perform a highly detailed electron tomography study on the FP, correlat e this with specific functions of the FP and then determine the effects of temperature and lifecycle progression on FP structures. This will enable me to understand how trypanosomes use their FP to perceive and respond to changes in their environment as they move between the mammalian and insect hosts. I will then combine reverse genetics with live cell imaging and molecular and cellular biology techniques to investigate specific questions relating to how some proteins are retained within th e FP whereas other proteins traffick freely to the bulk surface membrane. I will dissect the mechanism of protein retention within the FP and determine what role proteins signals, motifs and facilitator proteins play. I will also investigate the specificity of FP protein release that is observed under some conditions.