Don't miss our weekly PhD newsletter | Sign up now Don't miss our weekly PhD newsletter | Sign up now

  Structural and functional investigation of the human Vitamin C transporter.


   Department of Life Sciences

This project is no longer listed on FindAPhD.com and may not be available.

Click here to search FindAPhD.com for PhD studentship opportunities
  Prof B Byrne  No more applications being accepted  Funded PhD Project (European/UK Students Only)

About the Project

The human Vitamin C transporters, hSVCT1 and hSVCT2, belong to the Nucleobase Ascorbate transporter (NAT) family of proteins. hSVCT2 is key in the anticancer effects of ascorbic acid. hSVCT1 has been expressed in both Xenopus oocytes and COS cells and the protein used to study function and obtain a low resolution structure. However very little is known about these proteins, in particular how these differ in terms of substrate specificity and regulation compared with the NAT family proteins from bacteria and other eukaryotes. This project will initiate studies on the hSVCTs, designing and generating expression constructs and expressing the proteins in mammalian cells in order to allow us to obtain the most physiologically relevant material for study. The protein will be isolated using established detergent based extraction and purification protocols and the sample submitted to basic biophysical analyses to check for purity and stability. Earlier work in our laboratory has successfully stabilised a fungal NAT, UapA, for crystallographic purposes by the introduction of a single point mutation in the NAT signature motif sequence. We will attempt mutagenesis of the SVCTs based on this and other possible stabilisation sites. The most stable protein will be submitted to structural analysis using cryo-EM and if time and protein allows we will work with our collaborators at Kings College to attempt to understand the role of lipids in the structure and function of hSVCTs.  

The Department of Life Sciences at Imperial College London has funding for a PhD studentship, to commence 3rd October 2020.

We wish to widen participation and therefore we strongly encourage applications from individuals who completed their bachelor's and/or master's degrees at non-Russell group Universities. We are particularly keen to get applications from underrepresented groups (e.g. BAME candidates).

For candidates with a non-Russell group background, we are offering an online workshop (29 April) and Q&A (6 May) sessions where we will provide both information on life as a PhD student at Imperial, and advice and support for application and interview process for a PhD position. Candidates can register their interest in attending these events here

For information on the specific advertised project please contact the relevant supervisor (Professor Bernadette Byrne; [Email Address Removed]). For additional information on the general support provided to PhD students at Imperial College and within the Department of Life Sciences contact Rozan Hamilton-Nixon ([Email Address Removed]).

How to apply: Applications must be completed by submitting an online application form



Funding Notes

The studentships will cover UK tuition fees of £4,500pa and will provide an annual tax -free maintenance stipend of £17,609, in 12 monthly instalments. Studentships are expected to last for 36 months, subject to satisfactory progress. A BSc in biological, or related, sciences is required at Upper Second Class level or better and candidates with a Master's degree, in addition to the BSc, might be given preference. Candidates must be either UK or EU nationals with settled status, resident in the UK for at least 3 years prior to the commencement of the studentships. Non UK/EU nationals are not eligible.

References

Yilmaz Alguel, Sotiris Amilis, James Leung, George Lambrinidis, Stefano Capaldi, Nicola J. Scull, Gregory Craven, So Iwata, Alan Armstrong, Emmanuel Mikros, George Diallinas, Alexander D. Cameron, Bernadette Byrne*. (2016) The structure of UapA, a eukaryotic purine/H+ symporter, reveals a role for homodimerization in transport activity. Nature Commun. 7: 11336.
Albertina Velho and Simon Jarvis (2009). Topological studies of hSVCT1, the human sodium-dependent vitamin C transporter and the influence of N-glycosylation on its intracellular targeting. Exp. Cell Res. 315: 2312–2321.