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The University of Southampton
Structural Biology Part of Biological Sciences

Final year projects

Below are examples of final year undergraduate projects including scientific background and the type of experience you'll gain. Projects are listed by PI.

Ivo Tews

Project 1
Structure determination and characterisation of transporter proteins.
Generally, nutrients enter the periplasm via porines through the outer membrane. They are then transported into the cytoplasm by either low affinity ion driven transport systems or high affinity ABC-Transport systems. In the project you will express and purify ABC transporter SBPs using liquid chromatography methods. You will characterise the proteins, determine their ligands and measure binding affinities. You will then grow protein crystals, which are to be used for crystallographic structure determination.

Project 2
Cloning, purification and crystallisation of novel regulators of bacterial biofilm formation.
Bacteria are typically found in the motile planktonic life form, but they can become sessile and organise into biofilms and then evade host immune responses. This differentiation is controlled by the intracellular levels of cyclic diguanylate monophosphate, c-di-GMP. Enhanced c-di-GMP levels are associated with the biofilm mode of growth. In this project you will clone and purify the diguanylate cyclase and phosphodiesterase regions of MucR or NbdA (which regulate level of c-di-GMP), which will be recombinantly expressed in E. coli . You will then purify and crystallise the expressed proteins for the purpose of crystallographic 3D structure determination. You may also go on to characterise the activity of these domains through biochemical assays.

Project 3
Characterization of sensory input domains that control biofilm dispersal.
A number of different stimuli can regulate the formation and dispersal of bacterial biofilms, an antibiotic tolerant phenotype often involved in chronic infection. Many proteins are thought to directly couple stimulus input to downstream activity by detecting the stimulus in one domain and eliciting a conformational change to an effector domain in the same protein. PAS domains are a type of sensory domain known to be able to detect a range of inputs and are often found linked to biofilm regulating domains. This project will look at how PAS domains in Pseudomonas aeruginosa may detect stimuli and how these PAS domains may cause conformational changes that regulate biofilm behaviour. You will clone and purify PAS domains before crystallising these proteins and then identify the structural differences between the stimulated and unstimulated forms.

Project 4
Structure determination and characterization of  mutant Arabidopsis thaliana enzymes involved in vitamin B6 biosynthesis.

In most organisms, vitamin B6 biosynthesis is carried out by the Pdx1 protein. The enzyme catalyses a complex series of more than ten consecutive reactions. Substrates to the reaction are two sugars and ammonium salts. In the project you will mutate purify the A. thaliana protein using liquid chromatography methods. You will characterize the mutant enzyme kinetics by a spectrophotometric assay. You will then grow protein crystals, which are soaked with substrate solutions to allow the reaction to proceed within the crystal. Crystals prepared this way are to be used for crystallographic structure determination of intermediate states in the reaction cycle.

Project 5
Purification and crystallization of the Adam33 protease.
The membrane protein Adam33 has protease activity, which is required in airway modeling during lung development. ADAM33 mRNA and protein levels are increased in patients with moderate to severe asthma. The extracellular part of ADAM33 contains a metalloprotease domain that becomes catalytically active when the Pro-domain is cleaved. In the project, you will learn how to over-produce and purify this protein to homogeneity using liquid chromatography methods. The purified protease will be crystallised for 3D structure determination.

Medicine Project 6
Structure determination and refinement of antibodies that have potential in anti-cancer therapy (biologicals).
Monoclonal antibodies (mAb) have become a highly effective class of therapeutics. More than 30 are now approved for use in humans, targeting a range of different diseases. Much of the success of anti-cancer mAb derives from their high level of specificity, long biological half-life and ability to recruit numerous effector mechanisms. Appropriate FcR engagement leads to inflammatory mediator release and/or killing/phagocytosis of opsonised target cells. The outcome of mAb:FcR binding varies dependent on cell type, mAb isotype, and the balance of activatory or inhibitory signaling. It is clear that FcRs are key to regulating and co-ordinating responses from both innate and adaptive arms of the immune system. Research at UoS has recently delivered a panel of unique mAbs to both human and mouse FcRs with therapeutic significance, either activating or inhibiting receptor function. This project is concerned with refinement of x-ray crystallographic structures recently determined, and thus is computer based.

The final year in-depth project was the best part of my degree. I learnt and achieved so much and contributed to work that could change lives of cancer patients in the future. Amazing!

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