Professional projects

Over my prior positions I have been lucky enough to work in a diverse range of labs. As a result of this I have been able to experience and appreciate several different fields of life science research. This has also given me a broad understanding of multiple distinct techniques, expanding my tool box when encountering new problems. My skillset includes fundamental biological techniques such as PCR, western blotting, protein production, cell culture, and HPLC to more complex techniques including structural biology, mass spectrometry, isothermal titration calorimetry, spectroscopy, and many more. In addition to what I know, I am always keen to learn new techniques and ways to tackle interesting questions. 

I enjoy all aspects of life science from the fundamental research, to in-depth characterisation, to wide-screening, to searching for applications. During my later positions, my focus was on the design, production, analysis and understanding of proteins. These marvelous machines perform the majority of the cells functions and can increasingly be designed and harnessed in new and exciting ways for therapeutics or engineered effects. 

All of the work shown here has either been published or is shown with the permission of all parties involved. Please note that unpublished or confidential results cannot be displayed here. For this reason, the information shown on a few of the projects is sparse or absent entirely. This is by design and I apologise for the lack of detail. If you are curious, feel free to get in touch via the email at the bottom of the page and depending on circumstances I may be able to expand further. 

Pseudomonas aeruginosa is a noscomial pathogen that is responsible for a large number of hospital acquired infections. Compounding this issue is the fact that P. aeruginosa possesses strong innate antibiotic resistance through chromosomally encoded multi-drug efflux pumps. This makes treatment of infections highly problematic and the existence of these proteins enables quick acquisition of additional drug resistances. 

Cell surface fimbriae are essential in the primary colonisation phase of initial adherence to epithelial surfaces. P. aeruginosa possesses two distinct pili, the well characterised multi-functional type IV pilus, and the less studied TAD pilus, which is only involved in the adherence to lung epithelial cells. This project sought to understand how the structure of this pilus, as well as how binding to the cell surface is mediated. 

Amyloids are implicated in a wide range of human diseases including Alzheimer's. Amyloids are formed of soluble protein monomers aggregated into a fibrillar structure with the monomers arranged in a repeating β-sheet perpendicular to the direction of the fibril. Theoretically, all proteins can form amyloids, though only a few are known to cause disease. With the aging population, the incidence of Alzheimer's is only increasing. As a poorly understood condition, research into this field is vital to improve our knowledge and to possibly enable the development of treatments. 

Amyloid-β is formed from repeats of a peptide released from the amyloid precursor protein. These peptides form amyloidal protofilaments which in turn associate to form a double helical structure. This leads to variations in the pitch and rise of the helix. Amyloid-β presents as two distinct polymorphs with the pitch measured by the distance between the grooves of the helix, called the crossover distance (CD). 

We sought to characterise the two polymorphs through electron microscopy. We wished to observe their distribution and observe whether this distribution changes over a time course of assembly. We observed that in the later stages of assembly the filaments typically present with a longer CD indicating that this is a more stable formation of the filament. 

Gliomas are neurological tumours grown from cancerous glial cells. Glial cells are non neuronal cells that surround nervous cell tissue, maintaining homeostasis and forming myelin. Gliomas comprise roughly 30% of all neurological tumours. The prognosis for patients is poor, with even low grade tumours only having a ~50% 10 year survival rate, for high grade gliomas this is lower with a median survival rate of 3 years. Symptoms are heavily dependent on which region of the nervous tissue to glioma grows in, but can be severe. Given the slow growth rate of glial tissue, interventions such as chemotherapy can be less effective than for other cancers. Compounding this, given the inherently sensitive nature of their location, surgical intervention is difficult. 

The objective of this research was to see if herpes viruses could be used to selectively infect tumours and result in their shrinkage. This therapeutic intervention could then be combined with current radiotherapy, chemotherapy, and surgeries to improve prognosis, increase the success rate of treatments and hopefully save lives. Certain strains were observed to result in shrinkage, however, the specificity of the virus meant that these are not yet broadly applicable therapies. Nonetheless, viral therapies are promising and can stand to complement our existing repertoire of interventions. 

Given the use of animal models and the sensitive nature of this topic photos of this project have been omitted.