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Mathula Muhundan, a Laidlaw Scholar at the University of Toronto, seeks new ways to combat metabolic diseases.

Research Title: Exploring changes in brown adipocyte metabolism through comparative -omics analysis

Brown adipose tissue has gained prominence as a metabolic regulator over the past few years of research into treating obesity and other metabolically related syndromes such as type 2 diabetes. Brown adipose tissue expresses gene signatures and metabolic features (for example, the expression of mitochondrial uncoupler protein UCP1) that increase its thermogenic capacity in comparison to white adipose tissue. However, the heterogeneity of brown adipose tissue is such that more holistic methods of analysis are required to understand the effects of various treatments or transplantation of brown adipose tissue in the body for metabolic regulation and thermogenesis. This includes -omics methods that can extract data on a large scale about cell types in a sample under various conditions such as transcriptomics (gene expression), metabolomics (metabolites circulating in cells, such as small sugar molecules) and lipidomics (lipids and fatty acids in cells), as well as their potential role in function/dysfunction in disease.

I carried out differential gene expression analysis for a variety of datasets containing brown adipose tissue, with comparison to white adipose tissue as well as set contrasts over different days or different treatments. These analyses were carried out with transcriptomics data to visualize differences for known gene and metabolic markers through scatter plots as well as fold-change/BH-adjusted p-value analysis. I used and optimised a pipeline in the programming language R for the analysis, and with the conclusion of the main data analysis, I began further investigation into applying the pipeline to single-cell datasets rather than whole tissue datasets and using comparative methods in metabolomics and lipidomics in experiments such as stable isotope labelling to compare with the gene expression data obtained. 

Where did your passion for this research originate?

I like to tell people about my research in metabolism by comparing it to those scenes of people in movies or TV with a giant corkboard of red thread connecting evidence and trying to figure out the culprit. No matter how distant one metabolic pathway might seem from another, they’re all connected somehow. It’s part of what makes metabolism and metabolomics as a research field so exciting by doing such detective work, and its potential to unveil so much of human disease so profound. Sometimes there are multiple culprits too, with some popping up in certain situations (disease states), which makes the work even more intriguing! That’s often the case for widespread noncommunicable diseases, such as diabetes and cancer. Because the incidences of diseases such as diabetes have been rising over the past few years amongst diverse populations, and I personally have family members living with diabetes, I wanted to be able to use these tools to uncover potential mechanisms by which we can treat, and perhaps cure, type 2 diabetes. I have always been intrigued by medicine and the developing field of personalised medicine, and my hope is one day by better understanding unique metabolic states we can tailor therapeutics to the individual.

What is the most memorable moment from your Laidlaw scholarship experience so far?

The Laidlaw Scholars conference in Toronto last October! I remember being excited that the North American conference would be hosted at UofT and being eager to meet Laidlaw scholars from across North America and beyond. The people I met were beyond incredible and I’ve made connections with people I would have never met if it weren't for the program. I was amazed by the diversity of research topics and leadership in action projects fellow scholars are pursuing, and there’s something invigorating about being together with so many people passionate about a cause and making a difference.

What is the biggest challenge you came across in your research and leadership journeys so far, and what did you learn from it? 

I think the biggest challenge in my research journey thus far was learning new skills and adapting to the circumstances at the same time that I was conducting my research- but it was a challenge well worth it. I conducted my project remotely in Toronto in collaboration with the Tseng lab at Joslin Diabetes Centre and the Joslin Diabetes Centre Bioinformatics Core in Boston, Massachusetts. Being remote came with certain challenges that were not anticipated when I was beginning my project, such as accessing the data on the centre servers. I am also admittedly not advanced at coding, so trying to understand the transcriptomics analysis code using bioinformatics packages I never used before was daunting at first. I quickly realised however that my supervisor and the rest of the team were so patient and willing to help me grow and learn that the process became enjoyable, and I managed to establish a supportive working relationship with the team. Part of being a good leader is being a good team player and seeking support when you need it, and my research experience definitely exemplified that. 
 

Which particular leaders inspire you the most and why?

I’m always inspired by action in local communities first and foremost. I strongly believe that healthcare and environmental justice are very interconnected topics, and as such I appreciate the work that student leaders of several UofT groups in working to tackle these issues in Toronto. Student action has the potential to make changes at the governmental level and push issues affecting the entire community to the forefront of the political agenda. 

Briefly describe a scene from the future you are striving to create.

I hope for a future of global equality in access to healthcare services and knowledge. One of the first steps towards that is further research into healthcare problems and existing disparities that often go neglected. Healthcare is a basic human right, and it’s time that governments and organisations around the world prioritise it as such. That starts with empowering the next generation to be inquisitive about the biomedical and sociocultural aspects of healthcare, how they intersect and how to translate the knowledge we gain into meaningful action to ensure everyone has a high quality of life. 

What does it mean for you to be a Laidlaw Scholar?

If I had to describe my Laidlaw Scholar experience in one word, it would be resilience. I think resilience has come in so many forms throughout my journey- from being persistent in creating new opportunities for myself to explore research in an area I’ve been passionate about for years to getting through learning roadblocks when it comes to learning new skills - such as running a bash script that sometimes didn’t work because I accidentally indented a line I shouldn’t have. At the core of it all, though, is the Laidlaw support system- my amazing fellow scholars from the 2023 UofT cohort as well as the incredible UofT Laidlaw team and the support of the Laidlaw Foundation. I’m always learning something new from all the wonderful people around me in the community, and I think the community is such a valuable part of the experience. 

Quick-fire Questions

🎥 Currently Binging: Smiling Friends

📚 My top book recommendation: 

Soonish: Ten Emerging Technologies That'll Improve and/or Ruin Everything

🎶 My anthem: Throne by Bring Me The Horizon

🎵 Podcast obsession: 

White Coat, Black Art with Dr Brian Goldman

🌈 Something that made me feel joy recently: 

Visiting a cat cafe with my friends after final exams!