Dr Alex Mullins

Supervisor Details

Contact Details

Department of Chemistry, University of Warwick

Scientific Background

Research Interests

My research aims to combine bacterial genomics and chemical biology to guide natural product discovery and engineering. The vast and expanding databases of bacterial genomes provides an exciting opportunity to understand the evolution and diversity of natural products, providing novel insights into their biosynthesis.

Bacteria often group their genes together based on related functions such as the biosynthesis of specialised metabolites, known as biosynthetic gene clusters (BGCs). We can predict the presence of BGCs on bacterial genome, which acts as a gateway to further analyse their prevalence, distribution, and diversity using bioinformatic software.

My research encapsulates two tandem avenues: discovery and engineering:

Genome-guided discovery of natural products. Using a technique known as genome mining, we can exploit 100,000s of bacterial genomes to explore the diversity of related BGCs based on a small subset of previously characterised BGCs. This allows us to identify and characterise novel versions of these BGCs that leads to to discovery of novel natural products. The bioactive properties of these compounds can be investigated to determine the efficacy as antimicrobials, anti-cancer agents, and biopesticides.
Evolution-guided engineering of natural products. The same BGC is often found in multiple strains of the same species, or even multiple species of the same genus. By analysing hundreds of versions of the same BGC we can find natural splice variations in their genes that have occurred through recombination events. Excitingly, these gene splice variants encode for functional enzymes that biosynthetise variants of the original compound. We aim to explore these natural recombination events with the aim of replicating them in the lab to engineer novel variants of bioactive compounds of interest with enhanced efficacy.

Research Groups

Challis / Alkhalaf Group

Supervision Style

In three words or phrases: detail-oriented, supportive, guiding.

Provision of Training

I understand that a PhD is a learning experience and do not expect prospective students to be adept in every skill required for the research. I am happy to teach and guide students in developing new techniques and skills, and also encourage students to interact with other members of the group to enhance their training.

Progression Monitoring and Management

All group members have regular 1-2-1 meetings with their supervisory team, and also present at group meetings in rotation. The structure of 1-2-1 meetings will be tailored for individual student needs. I encourage students to structure and set day-to-day goals to advance the project, and show initiative in developing their research goals.

Communication

I appreciate that every student is different and I will customise my communication to optimise the student’s development.

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 month

In year 2 of PhD study

At least once per month

In year 3 of PhD study

At least once per month

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

Working Patterns

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 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:

Evolution-guided engineering of bacterial natural product biosynthesis

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).

Evolution-guided engineering of bacterial natural product biosynthesis

Secondary Supervisor(s): Professor Greg Challis, Dr Lona Alkhalaf

University of Registration: University of Warwick

BBSRC Research Themes:

Sustainable Agriculture and Food (Plant and Crop Science)
Renewable Resources and Clean Growth (Industrial Biotechnology)
Understanding the Rules of Life (Microbiology)
Integrated Understanding of Health (Pharmaceuticals)

Project Outline

Bacteria supply the world with an extraordinary number of useful bioactive compounds with uses in agriculture as pesticides and herbicides, and medicine as antimicrobials and pharmaceuticals. This breadth of functionality stems from the impressive structural diversity of these compounds that influences their size, composition, stereochemistry, functional groups, and cyclisation.

The lab exploits a genomic data-driven approach to discovering and engineering natural products by exploring the natural variations observed in Nature and harnessing these to manipulate biosynthetic gene pathways. Bioinformatics analyses (phylogenetics, genome mining, sequence comparison) provide insights into the evolution, diversity, and distribution of biosynthetic gene clusters. While downstream research combines microbiology, molecular biology, and analytical chemistry. This interdisciplinary approach is supported by close collaboration with other academics engaged in chemical biology research.

Current projects focus on the discovery and engineering of three classes of natural product: fatty acid-derived polyynes, polyketide-derived glutarimides, and non-ribosomal peptides (NRPs). Polyynes are structurally intriguing compounds with alternating single-triple C-C bonds, and possess antifungal and anti-Staphylococcus activity. Glutarimides possess antifungal and anti-cancer activity. NRPs are structurally diverse compounds biosynthesised by non-ribosomal peptide synthetases (NRPSs). NRPSs function as assembly lines with structured catalytic domain architectures. By mapping natural recombination events in these systems we aim to engineer these assembly lines to produce novel derivatives with altered bioactivity.

Aim

This genomics-driven PhD project will exploit bacterial genomics to identify and understand Natural recombination events in biosynthetic gene clusters. These events will be reconstructed, manipulated, and expanded in the lab to engineer novel assembly lines and biosynthesise novel natural product derivatives.

Techniques

This is an interdisciplinary project that will combine the following techniques:

Bacterial genomics (bioinformatics)
Microbiology (aseptic technique, antimicrobial activity assays)
Molecular genetics (cloning, TAR)
Metabolic profiling (LC-MS)
Metabolite purification (HPLC)
Structural elucidation (NMR)

Previous Projects (2024-25)

Primary supervisor for:

Evolution-guided engineering of bacterial NRPS systems