Taking on an Internship can help you progress towards your career goals. Here at the Career Development Services, we’re here to help you locate and undertake internships throughout the year. We run internships over the summer as part of our Summer Experience programme and after graduation, as part of our Bradford Graduate Programme. In an illustration of how taking on an internship can help you work towards your graduate career aims, a recent Pharmacology student expands on what he has gained throughout his work here.
- Why did you choose your particular internship?
Having had a keen interest in psychology and science as a teenager, a chance to carry out a research-based project in molecular neuroscience towards the end of my degree was an opportunity that I simply could not pass.
- What did you hope to gain from the internship?
My background is Biomedical sciences where I have been enrolled at the University of Bradford for the last three years, with an emphasis in Pharmacology. Throughout this period I have been able to study the biological processes that govern both Eukaryotic and Prokaryotic organisms as well as to develop laboratory analytical techniques to identify such processes. The course offered at Bradford also has a significant amount of time devoted to laboratory work. One such research-based module was Research topics II. It was here that I was first exposed to an active research laboratory and my research project focused on the biochemical analysis of the post-translational modification of Glutamate receptors and their relation to neurological disorders. This was also my first foray into the field of neurodegenerative research and through this I was able to meet other research groups present in the Norcroft laboratories. From the experience I gained during my research project and the interest in neurodegenerative research it sparked, I approached Dr Ritchie Williamson and proposed the idea of a six week research placement. This was made possible through joint funding through the summer experience program and Bradford School of Pharmacy.
- The technical bit: what did you learn through your internship?
Dr Williamsons’ laboratory focuses on understanding the molecular mechanisms that underlie neurodegeneration, with a particular focus on Alzheimer’s disease. One area that his lab is researching is the role of post-translational modifications in the pathogenesis of Alzheimer’s disease. A post-translational modification is where a protein is labelled with a specific moiety in order to alter its physiological function. Proteins can be post transnationally modified in a number of ways, such as phosphorylation, O-GlcNAcylation, acetylation and ubiquitination.
Alzheimer’s disease is clinically characterised by cognitive decline and memory impairment, and its neuropathologically distinct hallmarks include extracellular senile plaques containing amyloid-β-peptide, a toxic fragment of the amyloid precursor protein, and intracellular neurofibrillary tangles composed of hyperphosphorylated tau protein. Currently we do not know what cause Alzheimer’s disease, but there are a number of lifestyle factors that correlate with Alzheimer’s. Alzheimer’s disease is the most common cause of dementia among people with Type-2 Diabetes, while diabetes and impaired fasting glucose have been linked to increased risk of Mild Cognitive Impairment (MCI), considered a precursor to Alzheimer’s disease. The brain, much like every organ in the body primarily utilizes glucose as its energy source. However, as we age the brains ability to utilise glucose is reduced. This reduced glucose metabolism in the brain is exacerbated in Alzheimer’s disease. A potential link between the reduced glucose metabolism and Alzheimer’s disease pathology is protein O-GlcNAcylation, a post-translational modification that is dependent on glucose from a dietary source. In the context of Alzheimer’s disease however, contradictory results have been obtained in regards to cellular changes in the O-GlcNAc profile, with reports of either an increase or decrease in proteins
O-GlcNAcylation is entirely regulated by two key enzymes, O-GlcNAc Transferase (OGT) responsible for the addition of O-GlcNAc onto a specific protein, and β-N-Acetylglucosaminidase (OGA) responsible for its removal from proteins. Given the altered glucose metabolism and O-GlcNAc profile reported in Alzheimer’s disease the focus of my project was to determine concentration and dose responses of specific inhibitors of these two enzymes and to see if we could manipulate these levels in cellular models. This was achieved by carrying out various cell culture techniques to treat cell lines with inhibitors at different concentrations over a range of time points, focussing specifically on a experimental OGT inhibitor. After the treatment of these cells, the proteins were then isolated and quantified by various protein assays and analysed for the presence of O-GlcNAc modification using a techniques called SDS-PAGE followed by Western blotting. This process then allowed for the quantification of the amount of proteins bearing the O-GlcNAc modification. Quantitation of
O-GlcNAc signal was obtained by normalising to a house keeping protein. As a range of OGT inhibitor concentrations were used, our experimental protocol enabled us to find out which concentration was most effective at inhibiting OGT as well as for what treatment period.
- So what next? How has your internship helped you in the immediate scheme of things?
Once all the research results were obtained at the end of my placement period, they were formally presented at one of the regular research groups meetings. This was an exciting experience which enabled me to share my newly found knowledge through active research in the field of molecular neuroscience with scientists with years of experience.
- And in the bigger picture, how has an internship helped you?
Throughout this time period I learned many valuable lessons, not only ways to perfect specific techniques in order to obtain more accurate and reliable results, but also how to think like a scientist in order to progress my research further, eliminate anomalies and explain why certain pieces of data do not fit the proposed hypothesis. Having spent many hours in a research laboratory during my six-week placement period working independently, I successfully used several analytical techniques such as SDS-PAGE western blotting, Bradford assay, cell culture and harvesting to obtain valuable results which can be built upon for continued research in this area.
Due to the experience obtained throughout my placement period, I have now been offered an honorary contract by Bradford’s school of Pharmacy to continue with the research alongside my final year studies. Future work will determine the toxicity and efficacy of this approach to preventing the pathogenesis of Alzheimer’s disease. The experience gained will hopefully aid me in my long-term goal that is to undertake a PhD in the field of molecular neuroscience in the near future.