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Dr Alice Rothnie

Dr Alice Rothnie
Dr Alice Rothnie

Lecturer in Cell Biology/Biochemistry

Research Theme

Cellular and Molecular Biomedicine 

Research Centre

Aston Research Centre for Healthy Ageing (ARCHA)  

Profile

I joined Aston School of Life & Health Sciences in Jan 2009, having spent the previous two years as a postdoctoral researcher in Structural Biology at Warwick University, working with Dr. Corinne Smith on the mechanism of clathrin cage disassembly by the chaperone Hsc70.

Prior to this I held a postdoctoral fellowship at the Cancer Research Institute, Queen’s University, Kinston ON, Canada, working with Prof. Susan Cole on the interaction of MRP1 (multidrug resistance protein 1) with GSH.

I completed my PhD in the lab of Dr. Richard Callaghan at the Nuffield Dept. Clinical Lab. Sciences, John Radcliffe Hospital, Oxford, on the topographical changes of TM6 of P-glycoprotein.

Qualifications & Education

  • DPhil, in Biochemistry. Nuffield Dept. Clinical Lab. Sciences, University of Oxford. 2000-2004
  • MBiochem honours (2.1), in Biochemistry. Brasenose College, University of Oxford. 1996-2000

Employment

  • Jan 2010 – present: Lecturer in Cell Biology/Biochemistry. Aston University, Birmingham, UK.
  • Sept 2007 – Dec 2009: Post-doctoral researcher, Dept. Biological Sciences, Warwick University, Coventry, UK.
  • May 2004 – Aug 2007: Post-doctoral fellow, Cancer Research Institute, Queen’s University, Kingston ON, Canada. Recipient of a CIHR (Canadian Institutes Health Research) fellowship

Research interests

My research interests lie in elucidating the mechanistic, functional details of proteins that do important jobs in the cell, both in health and disease. To date these have included membrane transporter proteins of the ABC superfamily (ATP Binding Casette) involved in drug resistance in cancer, and the chaperone proteins involved in removing the clathrin coat from endocytosed vesicles, both of which use ATP hydrolysis to drive their function, and are closely associated with cell membranes.

My approach involves the overexpression and purification of the proteins, and subsequently putting all the parts back together to form an in vitro model system in order to study the function of these complex proteins. I use a wide range of biochemical functional assays and biophysical techniques to examine the mechanism, breaking it down into its constituent steps.

The type of questions I ask include; How does a protein recognise its particular substrate(s)? What effect does substrate binding have on the conformation of the protein? How is function coupled to ATP hydrolysis? How exactly does a protein carry out its job & what is the order of events that occur? How do disease causing mutations affect the function? Does the protein require interaction with other proteins to function? How is the process regulated? 

In the future I plan to use biochemical and biophysical methods to continue examining the mechanism of clathrin cage disassembly in more detail, and to study other members of the ABC family of transporters involved in human disease.

Membership of Professional Bodies

  • Biochemical Society
  • The Protein Society
  • Molecular Chaperone Club
  • Midlands Biophysics Network

Selected publications

  • Rothnie A., Clarke A.R., Kuzmic P., Cameron A. & Smith C.J. (2011) A sequential   mechanism for clathrin cage disassembly by Hsc70 and auxilin.Proc. Natl. Acad. Sci USA108; 6927-32
  • Maeno K., Nakajima A., Conseil G., Rothnie A., Deeley R.G. & Cole S.P.C (2009) Molecular basis for reduced estrone sulphate transport & altered modulator sensitivity of TM6 and TM17 mutants of MRP1 (ABCC1). Drug Metab. & Dispos. 37; 1411-20.

  • Conseil G., Rothnie A., Deeley R.G. & Cole S.P.C. (2009). Multiple roles of charged amino acids in cytoplasmic loop 7 for the expression and function of the multidrug and organic anion transporter MRP1 (ABCC1). Mol. Pharmacol. 75; 397-406.

  • Heikal A., Box K., Rothnie A., Storm J., Callaghan R. & Allen M. (2009) The stabilisation of purified, reconstituted, P-glycoprotein by freeze drying with disaccharides. Cryobiology 58; 37-44.

  • Rothnie A., Conseil G., Lau A.Y.T., Deeley R.G. & Cole S.P.C. (2008) Mechanistic differences between GSH transport by MRP1 (ABCC1) and GSH modulation of MRP1-mediated  transport. Mol. Pharmacol. 74; 1630-40.

  • Rothnie A., Callaghan R., Deeley R.G. & Cole S.P.C. (2006). Role of GSH in estrone sulphate binding and translocation by the multidrug resistance protein 1 (MRP1, ABCC1). J. Biol. Chem. 281; 13906-14.

  • Rothnie A., Storm J., McMahon R., Taylor A., Kerr I.D. & Callaghan R. (2005). The coupling mechanism of P-glycoprotein involves residue L339 in the sixth membrane spanning segment. FEBS Letts. 579; 3984-90.

  • Rothnie A., Storm J., Campbell J., Linton K.J., Kerr I.D. & Callaghan R. (2004). The topography of transmembrane segment six is altered during the catalytic cycle of P-glycoprotein. J. Biol. Chem. 279; 34913-21.

  • Martin C., Walker J., Rothnie A. & Callaghan R. (2003). The expression of P-glycoprotein does influence the distribution of novel fluorescent compounds in solid tumour models. Brit. J. Cancer 89; 1581-9.

  • Gabriel M.P., Storm J., Rothnie A., Taylor A.M., Linton K.J., Kerr I.D. & Callaghan R. (2003). Communication between the nucleotide binding domains of P-glycoprotein occurs via conformational changes that involve residue 508. Biochemistry 42; 7780-9.

  • Rothnie A., Theron D., Soceneantu L., Martin C., Traikia M., Berridge G., Higgins C.F., Devaux P.P. & Callaghan R. (2001). The importance of cholesterol in maintenance of P-glycoprotein activity and its membrane perturbing influence. Eur. Biophys. J. 30; 30-42.

Employable Graduates; Exploitable Research