I am working under the supervision of Dr Rebecca Notman and Dr Ann Dixon to study the structure of small oxetane-modified peptides, in collaboration with Professor Mike Shipman (funded by The Leverhulme Trust). I am using molecular dynamics techniques (Notman) to simulate modified and unmodified parent peptides (with and without NMR refinement), and comparing these to my experimental findings obtained using biophysical techniques such as 2D NMR and CD (Dixon).
So far my project has involved two main model systems: a small pentapeptide, which I have worked on both the linear and cyclic forms (to assess the effect of the oxetane modification on cyclisation), and a longer, helical peptide with and without the oxetane modification (to assess the effect of the oxetane on helical structures). I hope to work on a more biologically relevant model system in the coming months.
The NMR experiments I carry out use the high field NMR facilities at Warwick (Bruker Avance II 700 MHz), and I regularly run TOCSY, NOESY and 1H-13C and 1H-15N natural abundance HSQCs. Nuclear Overhauser Effect Spectroscopy (NOESY) experiments provide information about protons near to each other in space, so NOE correlations can be converted to distance restraints, which I impose in my MD simulations. Using NOESY techniques it is also possible to deduce whether specific secondary structure motifs are present in a peptide, by the presence or absence of certain long-range correlations. In this way, we were able to produce the first experimental evidence that introduction of an oxetane into a small peptide has a turn inducing effect (Roesner et al., 2019).
My MD work uses GROMACS and the CHARMM force field to simulate peptides with and without modifications. For most of my work so far I have been using brute force MD, although I am exploring the possibility of using advanced sampling techiques such as steered MD in order to simulate helical unwinding.
Roesner, S., Saunders, G.J., Wilkening, I., Jayawant, E., Geden, J.V., Kerby, P., Dixon, A.M., Notman, R. and Shipman, M., 2019. Macrocyclisation of small peptides enabled by oxetane incorporation. Chemical Science, Advance Article.
Powell, N.H., Clarkson, G.J., Notman, R., Raubo, P., Martin, N.G. and Shipman, M., 2014. Synthesis and structure of oxetane containing tripeptide motifs. Chemical Communications, 50(63), pp.8797-8800.
|Present||PhD in Chemistry||University of Warwick|
|2015 - 2017||
MSc in Genetic Manipulation and Molecular Cell Biology
|University of Sussex||Merit|
|2011 - 2015||
BSc in Biochemistry with Industrial/Professional Experience
|University of Manchester||2:1|
MSc Final Project, January 2017 - August 2017
"Co-localisation of TIP5 with Tau in Alzheimer’s Disease: Exploring a nucleolar role for Tau."
Supervised by Professor Louise Serpell (School of Life Sciences, University of Sussex).
BSc Final Project, January 2015 - May 2015
"Location of Tim-4+ Gastrointestinal Macrophages."
Supervised by Dr John Grainger (Manchester Collaborative Centre for Inflammation Research, University of Manchester).
Undergraduate Placement Year, September 2013 - August 2014
"Mechanisms of Uptake of Nano Iron in Hutu-80 Cells."
Supervised by Dr Dora Pereira (MRC Human Nutrition Research, Cambridge).
I'm an Associate Member of the Royal Society of Biology (AMRSB) and a member of the Biochemical Society. I regularly demonstrate 2nd and 3rd year chemical biology labs (gel electrophoresis) here at Warwick, as well as the occasional 3rd physical chemistry workshop. In the second year of my PhD I set up a weekly theoretical chemistry seminar series - feel free to get in touch if you'd like to present to us!
When I'm not working on my PhD, I'm a keen amateur baker, and love to experiment in the kitchen! I'm also a novice artist/calligrapher. I enjoy playing board games with friends, and spending time with my two cats.