Dr Felix Chan

Supervisor Details

Contact Details

Scientific Background

Research Interests

My main research interest is in neuroenergetics - what metabolic pathways and substrates drive our brain activity. To study this, I have focused on understanding metabolism in epilepsy.

Epilepsy presents as high-frequency repetitive firing of the neurons; which imposes considerable energetic demand on the brain; yet very little is known about what metabolic pathway sustain this incredibly challenging network activity. Additionally, some epilepsies have metabolic causes; some of which I have/currently studies; including mitochondrial epilepsy (in mitochondrial diseases like MELAS or MERRF) and mTORopathies like tuberous sclerosis complex (TSC). By understanding these various metabolic epilepsies, I hope to comprehensively understand the metabolic and mitochondrial aspect of epilepsy. Finally, I hope to leverage our understanding of metabolism in epilepsy to curate new targeted therapies for epilepsy using various approaches like pharmacological, genetic, or dietary interventions.

Scientific Inspiration

Prof. Ben Barres – He is a trailblazer in the field of glia research and also a forefront advocate for the LGBTQ+ community in science as an out trans man himself. When he was alive, he was also very kind and passionate about mentoring young people in science.

Research Groups

Chan Lab

Supervision Style

In three words or phrases: Compassionate, supportive, collaborative

Provision of Teaching

My approach is to work with you and the project at hand to develop a robust training plan to acquire the needed experimental skills in the lab. I am also passionate about development of ‘soft skills’ in science like project management, teaching and mentoring, and leadership; so I will endeavour to create and provide opportunities to nurture these skills.

Progression Monitoring and Management

I expect you to take ownership of the project and your progression; but will always be on-hand to provide support. We will have weekly 1:1 meeting to provide you private space to raise concerns or discuss issues relating to progress; but also weekly group meeting to foster teamwork.

Communication

To me, maintaining open and working communication stream is key to the success of your PhD. We have our own lab communication platform where we can directly message each other – occasionally, I may reach out to you out of hours but do not expect a reply from you until the next working hour.

PhD Students can expect scheduled meetings with me:

In a group meeting

At least once per week

In year 1 of PhD study

At least once per week

In year 2 of PhD study

At least once per week

In year 3 of PhD study

At least once per week

These meetings will be mainly face to face, and I am usually contactable for an instant response every working day.

Working Pattern

Certain tasks in my lab need to occur at set times, and students need to be able to commit to a rota/timetable shared with other members of the team.

Notice Period for Feedback

I need at least 2 weeks' notice to provide feedback on written work of up to 5000 words.

Project Details

Dr Chan is the primary supervisor on the below project:

The love triangle of immunometabolism: lysine, mTOR signaling, and immune response

Secondary Supervisor(s): Dr Ewan Ross

University of Registration: Aston University

BBSRC Research Themes: Understanding the Rules of Life (Immunology, Neuroscience and Behaviour)

Apply here!

Deadline: 23 May, 2024

Project Outline

mTOR signalling is an important metabolic signalling pathway that is implicated in aging and many diseases like cancer and neurodevelopmental diseases. The mTOR pathway regulates many important physiological pathways; including inflammation and immune response. Recently, Dr. Chan’s lab has found that lysine, an essential amino acid, is an important regulator of the mTOR pathway. Much is not known about the physiological role of lysine; but several studies varying lysine in animal’s diet changes the inflammatory and immune response, possibly linked to the mTOR pathway (Han et al, 2018; Huang et al, 2021).

Dr. Chan’s lab studies a rare neurodevelopmental disease with epilepsy called tuberous sclerosis complex (TSC) where the genetic mutation causes hyperactivity in mTOR. We have pilot data showing that lysine metabolism is increased in TSC and also, signatures of inflammation in the TSC brain. Specifically, we observed an increase in CCL5 expression, a receptor that has recently been linked in microglia-neuronal communication (Festa et al, 2023). This suggests that microglial immune response could drive the neuronal activity in the brain and potentially be linked to the epilepsy in TSC. Dr. Chan’s pilot data has also demonstrated that accumulation of lysine metabolite in the TSC brain lead to neuronal hyperactivity; however, it is unclear if this increase in lysine metabolism is driven by or drives the microglial or immune response in the brain.

Thus, this project aims to understand the link between immune response, lysine metabolism, and mTOR signalling. While our ultimate goal is to understand the physiology of this immune-metabolic signalling, results from this project may have relevance towards understanding the disease TSC. The cellular models of TSC in Dr. Chan’s lab; including the induced pluripotent stem cell models; will be invaluable tools to understand the influence of mTOR activity on these fundamental processes.

This project has two main objectives:

To understand bidirectional relationship between lysine metabolism on mTOR signaling in immune cells of macrophage and microglial lineage
To characterize the effect of immune signalling via CCL5 on neuronal activity and lysine metabolism in the brain

This project uses in vitro cell culture models developed in Dr. Chan and Dr. Ross’s lab. The student will work on primary cell culture models (mouse neurons and glia) as well as immortalized cell culture models (macrophage lines). Pharmacological tools will be used to manipulate lysine metabolism, mTOR signalling, and/or immune response (CCL5 signalling) in the cells. To validate some of these findings, we will also use genetic modification tools like CRISPR-Cas9 or siRNA to understand the effect of genetic knockdown/knockout on the immunometabolic signalling. Finally, the last stage of this project will validate the fundamental immunometabolic signalling we characterise on a human induced pluripotent stem cell (iPSC) model to understand human neuron-microglia immunometabolic signalling.

Techniques

Cell culture (primary and immortalized cell culture, iPSC cell culture)
Molecular biology (qPCR, Western Blot, etc)
Genetic modification (CRISPR-Cas9 or siRNA)
Flow cytometry