Dr Alexander Taylor

Profile

I am a Research Fellow in the Astbury Centre for Structural Molecular Biology, with a background in biochemistry, biophysics, and computational/mathematical biology. Initially, I did an undergraduate masters (MBiolSci) in Molecular Biology at the University of Sheffield (2012-2016), in which I specialised in biochemistry, biophysics and computational techniques. I then went on to do a PhD in biophysics with Dr. Rosie Staniforth and Prof. Per Bullough, also at the University of Sheffield (2016-2021), in which I used analytical theory, experiments, and simulations to study the nucleation of amyloid fibrils. During this period, I developed an enduring interest in using theoretical biophysics to understand protein conformation and self-assembly, and since then my work has been an approximately even split between theory and experiment. After my PhD, I joined the University of Leeds as a Research Fellow in Biochemistry and Biophysics (2022-present), where I am based in the laboratories of Prof. Sheena Radford (School of Molecular and Cellular Biology) and Dr. Richard Foster (Chemistry). I am involved in several research projects, all of which broadly concern the nucleation and structural evolution of amyloid fibrils formed by peptides and intrinsically disordered proteins (IDPs).

Research interests

My research focuses on the disordered (or partly ordered) states of proteins (including intrinsically disordered proteins, folding intermediates and many peptides), and the mechanisms by which they aggregate to form amyloid fibrils. Intrinsically disordered proteins and amyloid fibrils are involved in widespread health conditions such as Alzheimer’s disease, Parkinson’s disease, and type-2 diabetes, but are challenging to study as they exhibit a high degree of conformational heterogeneity, and populate short-lived states that are difficult to observe but can play a crucial role in misfolding and aggregation.

On the experimental side, I use techniques from biochemistry, biophysics and chemical biology (eg. biochemical assays, mass spectrometry, MALS, FIDA/AF4, SPR, EM, CD, HPLC, peptide synthesis). On the theoretical side, I use analytical theory (eg. chemical kinetics, thermodynamics, statistical mechanics, polymer theory) and simulations (esp. kinetic modelling, Monte Carlo, Langevin dynamics) to make sense of the data. I also work closely with specialists in solution-state NMR spectroscopy and cryo-EM, who provide further detailed information on the monomeric (/oligomeric) and amyloid states, respectively.

At present, my primary project involves the identification and characterisation of small molecule drugs (or leads for drug development) that alter the kinetics, mechanism, and structural outcomes of amyloid formation by the islet amyloid polypeptide (IAPP, also known as amylin), whose aggregation is involved in the onset of type-2 diabetes. In addition, I contribute to other ongoing projects on proteins involved in diseases such as Alzheimer’s and Parkinson’s, which have similar mechanisms of aggregation.

Qualifications

• PhD in Biophysics, Sheffield, 2021
• MBiolSci in Molecular Biology, Sheffield, 2016