Project 1: "Functional Amyloids: Investigating the Dynamics of Somatostatin Aggregation and Release"
Supervised by Dr Paul Wilson (Chemistry)
It is well-documented that many proteins have the ability to form insoluble, β-sheet rich protein aggregates known as amyloids. Pathogenic amyloids are ubiquitously discussed in scientific literature due to their association with neurodegenerative diseases such as Alzheimer’s and Parkinson’s. This project focused on functional amyloid aggregation, whereby the aggregation process is essential in allowing key physiological processes to occur in-vivo. Functional amyloids are known to aggregate reversibly, much unlike known pathogenic amyloids; this reversibility also contributes to the functionality of the amyloids.
Somatostatin-14 (SST) is neuropeptide hormone responsible for broad inhibitory effects on endocrine secretions in the brain, pancreas and gastrointestinal tract. SST has been reported to self-assemble into a functional amyloid structure both with and without the presence of a glycosaminoglycan (GAG). GAGs such as heparin are sulfonated polymers that have been strongly associated with the acceleration of both functional and pathogenic amyloid formation in-vivo. The negatively charged sulfate groups in heparin are thought to bind to positively charged amino acids residues (lysine and arginine), altering the peptide’s structure and thus accelerating its propensity to aggregate. Despite recognising these associations, our understanding of how the presence of GAGs affects the self-assembly mechanism by which peptides/proteins aggregate is limited.
The main aim of the project was to determine if SST aggregation could be induced ex-vivo and to investigate the effect of NaCl solution and the presence of five synthetic heparin-mimicking polymers on the kinetics and dynamics of the peptide aggregation. Thioflavin T dye, commonly used in biophysical studies of peptide aggregation, was added to the SST samples to monitor any amyloid formation over time using UV-vis fluorescence.
2017/18 - MChem Research Project: "Surface Enhanced Raman Spectroscopy (SERS) for the Detection of Formaldehyde in Aqueous Solution'
Supervised by Dr Nikola Chmel - Warwick Biophysical Chemistry
Pharmaceutical excipients are key, inert components of many formulations which contribute significantly to medicinal safety and efficacy. Formaldehyde is a common reactive impurity that forms over time within many commonly used drug excipients. This is a significant problem for the pharmaceuticals industry as the presence of impurities like formaldehyde degrade active drug ingredients, thus reducing the drug quality and shelf life. Raman Spectroscopy is a technique that can provide a non-destructive, unique vibrational fingerprint of analyte molecules. However, hindered by a weak signal intensity, it can be amplified by a modified technique, Surface Enhanced Raman Spectroscopy (SERS), a core technique in this report. The aim of this project was to explore the use of functionalised silver and gold nanoparticles to quantitatively detect formaldehyde in aqueous solution using SERS.
2017 - MRC IBR Summer Project: "Determination of Kif15-Tpx2 Binding Interfaces Using Cross-Linking Mass Spectrometry"
Supervised by Professor Andrew McAinsh - Warwick Medical School (CMCB)
An array of proteins are involved in the initiation, mediation and completion of cell division. Kinesins, are a family of motor proteins that are heavily involved in the mitotic process. This project specifically focuses on Kif15, a motor protein responsible for the maintenance of the bipolar spindle. Previous investigations have shown that microtubule-associated protein, TPX2, is responsible for localising Kif15 to the spindle MTs, allowing it to maintain the mitotic spindle. Additionally, studies have found that interactions between Kif15 and TPX2 can inhibit Kif15's motility along MTs, hindering its role within bipolar spindle assembly.
The focus of this project was to ascertain the binding interfaces between Kif15 and TPX2 using Cross-Linking Mass Spectrometry, to gain a clearer understanding of the mechanism by which TPX2 inhibits Kif15's motility along MTs. Kif15 has the potential to become a future therapeutic agent against cancer if the mechanism of its motility inhibition is understood further.
2015 - URSS Summer Project: "Investigating the Photochemistry of Methyl Anthranilate"
Supervised by Professor Vas Stavros - Warwick Physical Chemistry
Using femtosecond gas-phase pump-probe spectroscopy, the ultrafast dynamics of methyl anthranilate were studied through the irradiation the sample with UV radiation. Whilst in an electronically excited state, time-resolved velocity map imaging and photoelectron spectroscopy methods were used to determine potential relaxation pathways. Determining the specific relaxation pathway allows us to understand how the molecule would behave as a potential sunscreen.
First Class (Honours) in MChem Chemistry at University of Warwick
- Amsterdam Marathon Challenge Leader for Warwick Raising and Giving (RAG) - 2016/17
- Fundraised £1200 for The Children's Society
- Completed the Amsterdam Marathon
- Secretary and Equal Opportunities Officer for Warwick ChemSoc - 2015/16