Postgraduate Profiles

Gavin Knott

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Thesis: Understanding a multifunctional protein family: Exploring DBHS protein molecular interactions

The Drosophila behaviour/human splicing (DBHS) proteins are a family of obligatory dimeric proteins found in higher order mammals down to the simplest invertebrates. While most nuclear proteins can be assigned a name that clearly encompasses their function, such as ‘transcription factor’, ‘export factor’ or ‘polymerase’; for DBHS proteins, no such clean-cut title exists. The DBHS proteins are a multifunctional family regulating transcriptional initiation, the processing and export of RNA, maintenance of genomic DNA, nuclear pH homeostasis, subnuclear body formation and carcinogenesis. To complement this array of functions, they are reported in binding a diverse range of RNAs and both single and double stranded DNA. As a result it is difficult to establish a coherent picture for their nuclear activities.

My PhD is centred on unravelling this phenomenon by investigating the macromolecular interactions of the human DBHS protein family. This project involves the use of techniques such as cloning, protein expression and purification, biophysical characterisation and X-ray diffraction.

Why my research is important

There is a growing appreciation for the fundamental significance of DBHS proteins in human health and disease. Understanding how these proteins interact with each other and with their other molecular partners will undoubtedly shed light onto the complex issue of how DBHS proteins are able to participate in such a wide range of nuclear activities. Furthermore, this information will be vital for future rational design of anti-cancer therapeutics.