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WMS Events Calendar

Wednesday, February 05, 2020

BMS Divisional Seminar by Professor Lawrence Young, Dr Samuel Dean, Division of Biomedical Sciences, Warwick Medical School, University of Warwick
GLT2, Warwick Medical School

Professor Lawrence Young

Dissecting the role of the tumour microenvironment in EBV-associated nasopharyngeal carcinoma

Abstract: The cancer mass represents a dynamic landscape where a heterogenous population of tumour cells interact with a variety of infiltrating host cells, extracellular matrix proteins and secreted factors. This tumour microenvironment (TME) influences the development, growth and spread of cancer while also shaping therapeutic responses. Nasopharyngeal carcinoma (NPC) is an undifferentiated tumour with an extensive but ill-defined TME comprising infiltrating T cells, NK cells, macrophages and fibroblasts. The precise role of the TME on the growth and invasiveness of NPC is unknown but it is likely that these infiltrating cells provide an essential support to the growth and survival of the tumour cells. The unique geographic distribution of NPC in China and South-East Asia, along with the presence of latent Epstein-Barr virus (EBV) infection in every tumour cell, provide insights into the aetiology of this particular malignancy. The TME may support the maintenance of stable EBV infection in carcinoma cells and create an immune suppressive milieu that facilitates immune evasion. Better definition of the TME in NPC and its relationship to EBV infection will improve our understanding of NPC pathogenesis and support the development of novel therapeutic and preventative interventions.

Dr Samuel Dean

Flagellum composition and function in protozoan parasites

Abstract - Trypanosomatids are microscopic vector-borne parasites that cause wide-spread human and animal diseases. They currently infect ~17 million people, kill 80,000 people annually and are a terrible agricultural and economic burden upon developing counties. There is an urgent need for new therapies because no vaccines are available and existing drugs are often ineffective and toxic.
Central to their ability to spread and cause disease is a protrusion of the surface called the flagellum. The flagellum is essential for parasite movement and host-parasite interaction, and flagellum function is required for parasite virulence and transmission. Flagella have three distinct domains defined by the arrangement of their microtubules: the basal body that is embedded in the cytoplasm, the axoneme that protrudes from the cell body, and the transition zone (TZ) that links the two.
The axonemes of most motile flagella contain a central pair (CP) of microtubules that extend from the TZ and are essential for flagellum beating; defects in the CP cause the human pathologies hydrocephalus and primary ciliary dyskinesia. Further, in recent years the TZ has emerged as central to flagellum function and it is the location of many of the proteins and complexes that are implicated in a class of human genetic diseases called ‘ciliopathies’.
My research has used a novel proteomics method specifically designed to isolate insoluble cytoskeletal structures for proteomics analysis. Using this methodology, I determined the composition of the trypanosome TZ and discovered that two of its proteins act as CP nucleating factors.
My lab will focus on addressing the following questions:
1) How do trypanosome TZ proteins nucleate the CP microtubules?
2) What is the role of the TZ in other flagellum functions?
3) What is the role of the metazoan orthologs of trypanosome TZ proteins in ciliary function and human disease?