Pyruvate Dehydrogenase Complex Deficiency

GROUP G

HYPOTHESIS

In this project we will be exploring the enzymes which regulate pyruvate metabolism in the human body. We will use biochemical and mathematical methods to analyse the protein-protein interactions that occur within the pathway. Studying these interactions will allow us to investigate the causes of pyruvate dehydrogenase complex deficiency, a rare metabolic disorder affecting the body's ability to convert of pyruvate to acetyl-CoA for energy generation. Furthermore, we will be analysing the effect of a lipoic acid diet on the build-up of lactic acid, a major characteristic of pyruvate dehydrogenase complex deficiency.
We hypothesise that a high lipoic acid diet will be effective in reducing lactic acid build up in the body, therefore reducing complications involved with pyruvate dehydrogenase deficiency.

BACKGROUND INFORMATION

Pyruvate dehydrogenase complex deficiency (PDCD) is a rare disorder which affects energy metabolism in mitochondria. It is caused by defects in the pyruvate dehydrogenase (PDH) complex which is responsible for the conversion of pyruvate to acetyl-CoA. The most common symptom of the disease is a build-up of lactic acid which causes a range of problems in the body. Currently, there are no specific treatments for PDCD. Our target proteins, DLAT, LIAS, LIPT1 and NFU1, are involved in the metabolism of lipoic acid, which acts as a cofactor for the PDH complex. To explore the protein-protein interactions in the pathway, a number of mathematical graph analysis techniques were used, including centrality, community finding, modularity and the Louvain method.

INTERDISCIPLINARY STRATEGY

Our team consisted of four mathematics students (Gaspard, Ewan, Alex and Rezwan), and four biochemistry students (Billy, Minulee, Ally and Fiona). The key strengths of the mathematics students were conducting computational analysis on a protein network. The primary focus of the biochemistry students was developing hypotheses, investigating the disease/pathway, assessing the biological relevance of proteins found through network theory, and designing appropriate experiments. Evidently, the mathematics students had little to no biochemical understanding and the biochemistry students were faced with the same issues regarding understanding the mathematical content. Hence, our group needed to collaborate effectively during the semester to ensure that each student understood the content and was able to contribute to the project productively.

EXPERIMENTS

Mathematical Experiments

Each week, the biochemical students would provide the mathematics students with an area of interest regarding the deficiency we were studying (PDCD). Through computational processes, the mathematics students were able to conduct in depth studies into the proteins in order to maximise the information available for analysis.

Biochemical Experiments

We used a series of different experimental techniques and models to analyse the protein-protein interactions involved in pyruvate dehydrogenase complex deficiency. Our experimentation investigated our target proteins and related proteins found by the mathematics students, to understand the causes and potential treatments of the disease.

Conclusions

Overall, using key biochemistry and mathematical methods, we were able to successfully study pyruvate dehydrogenase complex deficiency (PDCD) and its impacts on an individual's health. Through analysing target proteins, and developing experimental procedures with different biological cell lines, we were able to observe the mechanisms involved within the pyruvate dehydrogenase complex (PDC) and investigate treatments to reduce implications of PDCD.

WANT TO KNOW MORE ABOUT OUR TEAM?

Working in a team of individuals from such different fields proved to be a massive challenge throughout our 12 week project. Through weekly collaboration, we were able to complete it to a high standard. Find out how we all contributed to the project by clicking on the button below!

8

TEAM MEMBERS

12

WEEKS TAKEN TO COMPLETE THE PROJECT