Professor Bruno Frenguelli

Supervisor Details

Contact Details

School of Life Sciences, University of Warwick

Scientific Background

Research Interests

The lab’s focus is on how a class of molecules known as the purines affect the brain and nervous system, and how they can be used to both diagnose brain disorders and as novel treatments. The most important purines are ATP – the energy source used by all cells, including brain cells, and adenosine – the “A” in ATP. When the brain faces high energy demand, eg during epileptic seizures, or a disruption in the supply of blood, such as during stroke, ATP is consumed, liberating adenosine, which switches off energy-demanding process. In doing so adenosine tries to preserve ATP levels and to protect the brain during these conditions. Importantly, the production of adenosine during these events in the brain results in the appearance of adenosine and its breakdown products in the blood stream. While this may be used to diagnose stroke and other brain injuries, this loss from the brain of these molecules denies the brain of the ability to re-make ATP from them. Part of the research effort in the lab is to try and restore the brain’s ability to make ATP through the provision of simple, safe and cheap ingredients already in use in humans. Another part of the effort is to work with a company, ZP, developing sensors to detect purine-based biomarkers for brain injury. An additional aspect of the lab’s purine research involves a novel molecule we have discovered that, like adenosine, has painkilling properties, but is devoid of the effects on the cardiovascular system and respiration. These side-effects have prevented development of such adenosine-based molecules as painkillers. We hope that this compound and its derivatives, which we have patented and licensed to a drug-testing company, will be of value in the development of new, non-opioid analgesics.

Scientific Inspiration

I watched a lot of science telly as a kid (eg Horizon, Connections, Cosmos, Life on Earth, Sky at Night, RoyaI Institution Xmas Lectures, The Body in Question, The Mind Machine), so I guess the presenters especially Carl Sagan (Cosmos), Colin Blakemore (The Mind Machine), Jonathan Miller (The Body in Question) and David Attenborough (Life on Earth) were major sources of inspiration.

Research Groups

Frenguelli Lab

Neuroscience

Behaviour, Brain and Society

Supervision Style

In three words or phrases: supportive, outcome-oriented, inclusive.

Provision of Training

Depending on the availability of experienced lab members, I will take responsibility for your technical training at first, leading to more independence and the opportunity to demonstrate technical and intellectual initiative as the project progresses.

Progression Monitoring and Management

I like to be kept up to date with project developments and will expect to see evidence of technical competency and experimental results on a weekly basis, at least initially. This is to ensure that the project gets off to a good start and remains on the track that we both agree on.

Communication

I prefer face-to-face communication, in person or over Teams/Zoom, but will use emails, including out-with typical working hours, to communicate with lab members, especially if a message needs to go to several people.

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 face to face, and I am usually contactable for an instant response on every working day and at weekends. Sometimes this may not be possible if I’m away, but I do try to respond promptly.

Working Patterns

Much of the work in my lab requires being present in the laboratory during the core hours of the day. This is in order to make best use of experimental tissue, the sharing of experimental and data analysis practice, and to have access to me and other lab members. Working form home is possible, eg on data analysis or writing, but apart from the final PhD thesis, much of this is best done on site so that any queries that arise can be addressed promptly.

Notice Period for Feedback

Since I have competing teaching and admin pressures on my time (as do all other academics), ideally material should be submitted the sooner before a deadline the better to allow me time to read the material, discuss this with you and revisions made prior to any deadline. As a ballpark, at least 2 week’s notice before a deadline to provide feedback on written work of up to 5000 words.

MIBTP Project Details

Current Projects (2025-26)

Primary supervisor for:

Investigating brain energy metabolism with mass spectrometry

See the PhD Opportunities section to see if this project is currently open for applications via MIBTP.

Please Note: The main page lists projects via BBSRC Research Theme(s) quoted and then relevant Topic(s).

Investigating brain energy metabolism with mass spectrometry

Secondary Supervisor(s): Dr Andrew Bottrill

University of Registration: University of Warwick

BBSRC Research Themes:

Understanding the Rules of Life (Neuroscience and Behaviour)
Integrated Understanding of Health (Ageing)

Project Outline

The brain is very reliant upon a constant supply of oxygen and glucose for the mitochondrial synthesis of ATP to meet the high metabolic demands of neuronal activity. During instances when this supply is interrupted or when the ATP demands of neuronal activity outstrip the synthesis of ATP, the brain utilises a biochemical pathway that salvages ATP metabolites for resynthesis into ATP. Importantly, the metabolism of ATP yields a molecule (adenosine) that acts to reduce neuronal energy demands, while the resynthesis of ATP via the salvage pathway can be enhanced by providing brain tissue with the two primary components of adenosine, ribose and adenine.

In this project we will use imaging approaches based upon mass spectrometry to follow ATP and its metabolites through the salvage pathway. This imaging approach involves using a laser to ionise molecules in brain tissue sections. These molecules are then analysed via the mass spectrometer to build up, pixel by pixel, an image of the location of molecules, in highly defined regions (~10 µm diameter spots), across entire brain sections. With this approach we can ask how the metabolic profile of the brain is affected changes in the supply of oxygen and glucose and intense neuronal activity, how the metabolic profile of the brain changes with ageing and age-related brain conditions, and whether supplementation with ribose and adenine, two compounds used in humans, can improve brain energy metabolism.

The project will involve training in imaging mass spectrometry and in vitro and in vivo approaches for the preparation of brain tissue samples.

References

Gessner P, Lum J, Frenguelli BG. The mammalian purine salvage pathway as an exploitable route for cerebral bioenergetic support after brain injury. Neuropharmacology. 2023 224:109370. https://doi.org/10.1016/j.neuropharm.2022.109370.

Frenguelli BG. (2019) The Purine Salvage Pathway and the Restoration of Cerebral ATP: Implications for Brain Slice Physiology and Brain Injury. Neurochem Res. 44:661-675. https://link.springer.com/article/10.1007/s11064-017-2386-6.

Previous Projects (2024-25)

Primary supervisor for:

Mass spectrometry imaging of brain energy metabolites Novel GPCR agonists with peculiar properties and translational potential for the treatment of pain