My Dissertation Experience: Lucia Garcia-Figueras Gonzalez

Supervisor and Project title: Professor Paul O’Shea. ‘Studying disease using interactome analysis; the innate immune system in Alzheimer’s disease’.

Why I chose this topic:

As a biology with psychology student, I was particularly interested in the biological aspect and understanding of the brain and the underpinned processes that mould behaviour or cause diseases. The brain is the most complex and mysterious organ, and very little is known about it. Alzheimer’s disease is the most common type of dementia worldwide. For this reason, I was interested in engaging with a project aiming to research the unknown disease. This has allowed me to work in an area that I am really interested in and contributing to a wider project aiming to cure Alzheimer.

Background to the Project: Alzheimer’s disease is the most common type of dementia, which is expected to increase in following years. Even though many drugs have been developed in order to alleviate its symptoms, there is no current cure. The reason for this may be that although age is highest risk factor, but there are other causes not yet known. Molecular, genetic and environmental causes affect its onset. The two theories that have being juggled for years and are known to be involved in the development of the disease are the Aβ plaques accumulation and the tau tangle formation. However, other theories have been widely recurrent in the last decades, like the neuroinflammation hypothesis, which postulates that the disease may be closely related to the immune system and its processes.

What was the aim of the Project? The three main aims of the project are getting a wider understanding of Alzheimer’s disease and the mechanisms underlying its development; the selection of target molecules that allow for new drugs to be developed; a more accurate definition of diagnostic targets before the symptoms begin.

How much time I spent in the lab? As a dry project, no time was spent in a laboratory. Instead, the data gathering was made through a computer programme (VisAnt). The programme was used in a few weeks, as the large amount of data could make the research endless. The amount spent gathering data was in a couple of weeks until all the data necessary was taken.

What I investigated: the ‘small world effect’ is the theory that states that any two people in the planet are connected by a chain of people. The research project is based in this theory but applied to biological molecules. The programme used allows to build connections between all the molecules in the chosen organism, as they are all connected in some way. Previous studies had shown the involvement of 12 molecules in Alzheimer’s disease: PDCD4, PSEN1, NOS3, APP, IGHM, RAB3A, CASP1, TREM2, SYK, TYROBP, MAPK11, IFIT3, ZAP70 and FBXL12.  My job was to observe how these were connected through other molecules, as well as analyse the biological pathways. The less molecules are between 2 of the prospective molecules, the more probability there is that their pathways are connected, and the more probability that specific molecule is involved in the cause of the disease.

What I discovered: the molecules which were closely connected to the prospective molecules in different ways were pointed out. A second filter was made in terms of the pathways these were involved in: the ones taking part in the immune system or neurodegenerative diseases were selected. A few molecules, such as CYP2C8, which is mainly involved in metabolic pathways. The involvement of these molecules in pathways that are known to be directly related to Alzheimer’s disease may indicate that they are also involved, which makes them a potential target molecules.

If I could do it again, what would I change: doing the Project has been incredibly useful for developing many skills, such as scientific writing, data interpretation, research and, in this case, VisAnt basic skills. These skills, along with the opportunity to work independently were very valuable and look good on the CV.

Any hints or advice? A piece of practical advice is to write the report’s sections, particularly the methods and results, not after gathering all the data, but while doing so. This way will avoid any unnecessary stress before the deadline. The second advice is to ask as many questions as you want to your supervisor.