Dr Lona Alkhalaf

Supervisor Details

Contact Details

Department of Chemistry, University of Warwick

Scientific Background

Research Interests

The main research focus of the group is the chemistry and biology of natural products e.g. antibiotics, anticancers, herbicides, and other bioactive metabolites.

Research in the group encompasses diverse aspects of the chemistry and biology of natural products, including genomics-driven discovery of new bioactive metabolites, elucidation of novel pathways for natural product biosynthesis, mechanistic enzymology of unusual biosynthetic enzymes, biosynthetic engineering approaches to the production of novel natural product derivatives, the total synthesis of the natural products we discover, and elucidation of the biological functions of natural products.

Research Groups

Challis / Alkhalaf Group

Supervision Style

In three words or phrases: supportive, student-centred, collaborative.

Provision of Training

I tailor my training strategies to the individual student. Students will progress towards becoming more independent throughout the PhD.

Progression Monitoring and Management

I tailor progression and monitoring management to the individual’s needs to ensure they make good progress throughout the course of the PhD. At a minimum we will meet with monthly to discuss progress and plan next steps, with more ad-hoc meetings when needed.

Communication

I tailor my communication style according to the individual’s needs. 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 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 a mixture of face to face and video chat or telephone. I am usually contactable for an instant response on every working day.

Work 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 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:

Structural and Mechanistic Characterisation of Bacterial Natural Product Targets

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).

Structural and Mechanistic Characterisation of Bacterial Natural Product Targets

Secondary Supervisor(s): Dr Matthew Jenner

University of Registration: University of Warwick

BBSRC Research Themes:

Sustainable Agriculture and Food (Plant and Crop Science)
Understanding the Rules of Life (Microbiology, Structural Biology)
Integrated Understanding of Health (Pharmaceuticals)

Project Outline

Natural products are a vital source of medicines and agrichemicals. For example, over 70% of the antibiotics on the World Health Organisation’s list of essential medicines are derived from natural sources (plants, bacteria or fungus). In order to develop natural products as pharmaceutical or agrichemical leads a detailed understanding of their mechanism of action is required. Our lab uses X-ray crystallography alongside other techniques such as chemical synthesis, analytical chemistry, bioinformatics and enzymology to understand how bacterial natural products interact with their targets at a molecular level.

A project in the lab will typically involve natural product isolation and structural characterisation by mass spectrometry and NMR spectroscopy, enzyme overproduction and purification, assay development, X-ray crystallography molecular modelling and bioinformatics to identify key residues involved in binding, mutagenesis of residues to test hypotheses, and/or synthesis of small molecule substrate mimics or mechanistic probes.

We are particularly interested in cases for which several different isoforms of a natural product are made by different bacteria and the evolutionary driving force for incorporation of these modifications. For example, plant associated bacteria produce diverse bicyclic depispeptide histone deacetylase (HDAC) inhibitors, including romidepsin, an approved anticancer drug. They contain both a conserved sulphur pharmacophore, that binds to the zinc in the active site of HDACs, and a variable peptide region. We hypothesise that bacteria have evolved to make structural variants of the same scaffold to target different isoforms of HDACs depending on their environment. We are currently working on determining the activity of several HDAC inhibitors against representative plant and fungal HDACs and using structural biology techniques to understand any differences at a molecular level.

Techniques

X-ray crystallography
Protein overproduction and purification
Enzymology
Small molecule NMR spectroscopy and mass spectrometry
Bacterial growth
LC-MS and HPLC
Bioinformatics
Chemical synthesis
Genetic manipulation
Protein mass spectrometry

Co-supervisor on projects with Dr Fabrizio Alberti and Dr Alex Mullins.

Previous Projects (2024-25)

Primary supervisor for:

Structural and Mechanistic Characterisation of Bacterial Natural Product Targets

Co-supervisor on projects with Professor Greg Challis and Dr Alex Mullins.