Identifying binding partners of CLEC14A and Molecular studies of NKG2D-ULBP interactions

Khan, Kabir Ali (2012). Identifying binding partners of CLEC14A and Molecular studies of NKG2D-ULBP interactions. University of Birmingham. M.Res.

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Abstract

Blood vessels associated with tumours express a whole range of different protein tumour endothelial markers (TEMs) compared to healthy vessels that can be exploited therapeutically. CLEC14A is a TEM that is highly expressed on tumour vasculature and absent in healthy tissue. CLEC14A is important for endothelial cell migration, vascular development in zebrafish and is expressed in response to low shear stress. However, very little is known about the molecular mechanisms involved in CLEC14A functions. In this study the extracellular domain of CLEC14A fused to a human Fc tag was used to identify possible protein binding partners.

The activating immune receptor NKG2D binds to the cellular stress ligand ULBP6 as a mechanism of NK and T-lymphocytes recognising cells that have undergone transformation or viral infection. There are two major alleles of ULBP6 (ULBP6*01 and ULBP6*02) with two amino acid differences between them. Recent studies suggest that the NKG2D-ULBP interactions play a critical role in potentiating curative anti-tumour responses after stem cell transplantation (SCT) in haematological malignancies. This study focuses on understanding the molecular basis of NKG2D-ULBP interactions using modelling, binding and structural approaches.

Type of Work:

Thesis (Masters by Research > M.Res.)

Award Type:

Masters by Research > M.Res.

Supervisor(s):