My current research is supervised by Dr Simon Mitchell, in collaboration with Professors Chris and Andrea Pepper.

The focus of my work is to characterise the molecular mechanisms causing diffuse large B-cell lymphoma (DLBCL) using a combination of computational and experimental techniques. DLBCL is an extremely heterogeneous diseases, with 60% of patients successfully cured by immunochemotherapy. For the remaining 40% of patients, the prognosis is extremely poor. 

In DLBCL, NFkB is constitutively active, but the roles of the individual NFkB subunits in lymphoma remain poorly understood. I have developed a flow cytometry analysis pipeline to characterise the abundances and activity of different NFkB subunits in DLBCL cell lines. We can feed this data into a systems biology model, allowing us to predict how different cell lines might respond to treatment or microenvironmental stimuli.

Under the supervision of Dr Rebecca Notman and Dr Ann Dixon, I studied the structure of small oxetane-modified peptides, in collaboration with Professor Mike Shipman (funded by The Leverhulme Trust). I used molecular dynamics (MD) techniques 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 .

The NMR experiments I carried out in this work used the high field NMR facilities at Warwick (Bruker Avance II 700 MHz), and I regularly ran 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 imposed 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 involved using GROMACS and the CHARMM force field to simulate peptides with and without modifications. I used classical MD techniques to simulate smaller peptides in tandem with steered MD in order to simulate helical unwinding in longer peptides. We have shown that oxetane modification is not tolerated in helical peptides, and were able to produce a model which replicates the experimental trend observed using biophysical techniques, as well as providing insight into the molecular determinants of this destabilisation (Jayawant et al., 2020).

I also did some work in this project to explore the impact of oxetane modification on antimicrobial activity.