Understanding Movement and Mechanism in Molecuar Machines (MACMILLANF2U20SF) at University of East Anglia on FindAPhD.com

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Dr F MacMillan No more applications being accepted Self-Funded PhD Students Only

About the Project

We study the architecture and functional dynamics of membrane proteins, especially many medically relevant membrane transport systems. There is increasing evidence that membrane proteins do not act alone, but that they are organised as nanomachineries which function through the concerted action of individual components with high precision and specificity observed in both time and space. We are seeking to unravel the principles underlying the architecture and dynamics of these protein nanomachineries as well as their function. Our experimental approach focuses on the use of magnetic resonance techniques specifically Electron Paramagnetic Resonance (EPR) and Nuclear Magnetic Resonance (NMR) spectroscopy in combination with molecular biological, biochemical and strucutrual biology approaches.

This PhD project will study cation diffusion facilitator (CDF) proteins which are a conserved family of divalent transition metal cation transporters. CDF proteins form dimers and are usually composed of two domains: the transmembrane domain (TMD), in which the metal cations are transported through a highly-conserved metal-binding site, and a regulatory cytoplasmic C-terminal domain (CTD). Each CDF protein transports either one specific metal, or multiple metals, from the cytoplasm. The nature of TMD metal binding sites correlates with metal selectivity in most CDF proteins, however in many proteins it is not the sole determinant. Here, the model CDF protein MamM, from magnetotactic bacteria, will be used to probe the role of the CTD in metal selectivity. Using a combination of biophysical (EPR) and structural (NMR) approaches, the dynamics of binding of different metals to MamM CTD will be characterized. The aim is to reveal that different metals bind distinctively to MamM CTD in terms of; their binding sites, thermodynamics and binding-dependent conformation through probing the functional dynamics of this protein using a combination of state-of-the-art magnetic resonance techniques.

For more information about the supervisor of this project please visit https://www.uea.ac.uk/chemistry/people/profile/fraser-macmillan

This is a Phd Programme

The study mode is full time and the start date is October 2020.

Acceptable first degree in Chemistry, Biochemistry, Biophysics, Physics or related. The standard minimum entry requirement is 2:1

Funding Notes

This PhD project is offered on a self-funding basis. It is open to applicants with funding or those applying to funding sources. Details of tuition fees can be found at http://www.uea.ac.uk/study/postgraduate/research-degrees/fees-and-funding.

A bench fee is also payable on top of the tuition fee to cover specialist equipment or laboratory costs required for the research. Applicants should contact the primary supervisor for further information about the fee associated with the project.

References

i) Anna Mullen, Jenny Hall, Janika Diegel, Isa Hassan, Adam Fey, Fraser MacMillan, Membrane transporters studied by EPR spectroscopy: structure determination and elucidation of functional dynamics. Biochem. Soc. Trans. 44, 905–915 (2016) .
ii) Shiran Barber‐Zucker, Jenny Hall, Sivasubramanyan, Venkata Mangapuram, Itamar Kass, Sofiya Kolusheva, Fraser MacMillan*, Raz Zarivach*, Arnon Henn*, Metal binding to the dynamic cytoplasmic domain of the cation diffusion facilitator (CDF) protein MamM induces a 'locked-in' configuration
FEBS Journal 286(11) 2193-2215 (2019)
iii) Shiran Barber-Zucker, Jenny Hall, Afonso Froes, Sofiya Kolusheva, Fraser MacMillan* and Raz Zarivach* The cation diffusion facilitator protein MamM’s cytoplasmic domain exhibits metal-type dependent binding modes and discriminates against Mn2+. Structure, submitted (2020)
iv) Shiran Barber-Zucker & Raz Zarivach, A Look into the Biochemistry of Magnetosome Biosynthesis in Magnetotactic Bacteria. ACS Chem. Biol. 12, 13–22 (2017).

Where will I study?

University of East Anglia

We’re one of the UK’s leading research institutions, ranked 10th in the UK for the quality of our research outputs and with more than 1,500 research students.

Understanding Movement and Mechanism in Molecuar Machines (MACMILLANF2U20SF)

University of East Anglia School of Chemistry