Dr Richard Hopkinson

Supervisor Details

Contact Details

Dr Richard Hopkinson

School of Chemistry, University of Leicester

Scientific Background

Research Interests

Research group activity

Understanding the functional role of formaldehyde in health and disease.

My research is focused on understanding how reactions between biomolecules and reactive small molecules, most notably formaldehyde, affect biological systems in health and disease. Formaldehyde, the simplest aldehyde, is a highly-reactive and often toxic electrophile that is a by-product of enzymatic demethylation reactions in human cells. The mechanisms underpinning formaldehyde toxicity are poorly understood, which is likely a consequence of its complex and uncharacterised reactivity with biomolecules, often involving unstable intermediates. My research uses chemical/synthetic, biochemical and cellular methods to identify and characterise the complex biologically relevant chemistry of formaldehyde with biomolecules. Ultimately, we hope to define the mechanisms underpinning formaldehyde homeostasis and biology in health and disease.

Research Groups

The Hopkinson Group

Supervision Style

In three words or phrases: Laid-back, spontaneous, inclusive.

Provision of Training

Your training will be supervised partly by myself but also by my experienced post docs and PhD students. I will take overall responsibility for your technical training at first, leading to more independence later.

Progression Monitoring and Management

I like to be kept up to date, and would like to be informed when new method development/data generation results emerge, preferably on a weekly basis. I am here for advice and guidance to help you reach the goals you set for yourself.

Communication

I have an informal and laid back communication style. I am known to email my team outside of regular hours, however I do not expect anyone to read or reply to them. I am happy to discuss any issues that are impacting your ability to fulfil your potential.

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

The meetings will be face to face and I am usually contactable for an instant response (if required) on every working day.

Working Pattern

The timing of work in my lab is completely flexible, and (other than attending pre-arranged meetings), I expect students to manage their own time.

Notice Period for Feedback

I need at least 1 week’s notice to provide feedback on written work of up to 5000 words.

MIBTP Project Details

Current Projects (2025-26)

Primary supervisor for:

Evaluating the impact of chemically reactive metabolites in premature ageing

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).

Evaluating the impact of genotoxic aldehyde stress in premature ageing

Secondary Supervisor(s): Dr Kayoko Tanaka

University of Registration: University of Leicester

BBSRC Research Themes:

Understanding the Rules of Life (Systems Biology)
Integrated Understanding of Health (Ageing, Diet and Health)

Project Outline

While most biological molecules are not that chemically reactive, some are very reactive and can significantly affect our health. Some reactive metabolites (RMs) are known toxins and carcinogens that act by damaging DNA and proteins. However, the vast majority of biological functions involving RMs are unknown.

We believe that RMs are key regulators of human biology. Given their chemical reactivity, it is likely that RMs can affect multiple biochemical pathways by reacting with DNA and proteins. However, it is currently unclear what reactions occur in human cells and how these reactions affect human biology at the molecular and systems levels.

Recent pioneering work has revealed a potential function for aldehyde RMs in human ageing. These studies using mouse models suggest a link between genotoxic aldehyde stress (as caused by aldehydes derived from alcohol and cigarette smoke) and the p53 response, leading to early cell senescence. This is a hallmark of premature ageing (Wang et al., Mol. Cell, 2023). While these findings are extremely exciting, there is currently little known about the underpinning molecular mechanism. Identifying this mechanism is essential as it would redefine our understanding of human ageing and could lead to the development of anti-ageing therapies.

Defining how RMs induce cell senescence requires the development of a simple and robust cell model where (i) cellular RM levels can be easily modulated and quantified, and (ii) where the molecular mechanisms underpinning senescence, e.g. p53-dependent pathways, can be analysed in a sensitive and controlled manner. This project aims to establish such a cell model and to use it to discover how RMs affect ageing-related biology.

Objective 1: To establish human cell lines where endogenous RM levels can be manipulated.

The project will generate cell models deficient in RM metabolism. In particular, we will focus on the metabolism of aldehyde RMs, with which we have extensive experience. Our cell models will be derived from immortalised but ‘normal’ cells (unlike normally used cancer-derived cells), which will make them ideal for studying senescence-related biological pathways in healthy models without inducing senescence. Derivatives of these cells will also be generated with single and double knock-outs of ADH5 and ALDH2, which are key aldehyde-metabolising enzymes. This will enable us to test how aldehyde metabolism affects ageing.

Objective 2: To develop methods to modulate and quantify cellular aldehyde levels.

The project will develop methods to both deliver aldehydes to cells and to quantify cellular aldehyde levels in response to aldehyde exposure and to knock-out of aldehyde metabolism enzymes. This work will build on existing research in the Hopkinson group with aldehyde-releasing small molecules and aldehyde detection methods. The releasers and detection methods will ultimately be used in cell assays (see below).

Objective 3: To study the effects of aldehydes on ageing-related cell functions

The project will determine the aldehyde sensitivity and aldehyde metabolism efficiency of the cell models using reported cytotoxicity assays and NMR studies on cell lysates. The project will also study the effects of aldehydes and aldehyde releasers (see above) on cell cycle progression and p53-dependent biological pathways. These studies will include analysis of p53 levels and downstream markers of p53 induction. Any changes will be correlated with aldehyde levels using the aldehyde quantification methods. The status of DNA damage will also be assessed, while later work will test whether combinatorial exposure to aldehyde releasers and p53 modulators induces synergistic effects. Overall, these studies will give unprecedented insight into the role of aldehyde in p53 biology and ageing.

Techniques

Techniques that will be undertaken during the project:

CRISPR-Cas9-mediated gene editing.
Cell culture.
Organic synthesis.
Spectroscopic techniques, most notably NMR spectroscopy and mass spectrometry.
Western blotting.
Cell cycle analysis, including flow cytometry.
Indirect fluorescence microscopy.

Previous Projects (2024-25)

Primary supervisor for:

Evaluating the impact of genotoxic aldehyde stress in premature ageing

Previous Projects (2023-24)

Primary supervisor for:

Treating bacterial infections using aldehydes