Dr Fabrizio Alberti

Supervisor Details

Contact Details

School of Life Sciences, University of Warwick

Scientific Background

Research Interests

Fungi represent an incredibly rich reservoir of natural products, which often show potent bioactivity and find applications in different fields, including medicine and crop protection. Research in the Alberti Lab aims to discover new molecules from fungi with useful bioactivities and understand how these compounds are assembled.

To this aim, we have recently developed a platform, based on Saccharomyces cerevisiae (baker's yeast), that accumulates increased amounts of precursors to a specific class of natural products called isoprenoid quinones.

We are also developing new synthetic biology tools to be used in basidiomycete (mushroom-forming) fungi that will enable us and the wider scientific community to exploit the genetic potential of this underexplored class of microorganisms.

Scientific Inspiration

One of my professional role models is Rita Levi-Montalcini, an Italian neurobiologist whose commitment and devotion to science I find particularly inspiring. During the Second World War she was banned from holding a university appointment due to the anti-Jewish laws, so she set up a lab in her own home and conducted research that set the foundations to her later work on nerve growth that led her to being awarded the Nobel prize in Physiology or Medicine in 1986.

Research Groups

Alberti Lab

Quantitative, Systems and Engineering Biology

Microbiology and Infectious Disease

Environment and Ecology

Supervision Style

In three words or phrases: Supportive, outcome-orientated, collaborative.

Provision of Teaching

Your technical training will be provided by senior team members (including myself, my Post-doctoral Research Associate and Senior Research Technician), in the first instance. Consequently, you will be expected to develop a more independent approach to your own training that will involve literature research, as well as discussions with colleagues and collaborators.

Progression Monitoring and Management

I monitor the progress of my PhD students through regular progress meetings. I like to be kept up to date with research, which can take place either through supervision meetings or presentations at group meetings. I like to have an agreed timeframe of experiments and outcomes with students. If progress is slower than expected, we will discuss a plan of action to take into account the reasons for it and come up with a revised strategy, as well as ways for you to be fully supported to achieve your goals.

Communication

Communication between me and you will take place primarily via emails, though my door is always open and my team members often knock at my office to ask for advice. I expect all my team members to have a good work/life balance and I never send emails out of standard working hours (e.g. evenings and weekends). We have a team’s WhatsApp group chat, which we regularly use to communicate lab matters.

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 fortnight

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 Pattern

Work in my lab requires being present on site (be it in a laboratory or at a field site) during the core hours of 9 am – 5 pm (or a subset if working part 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:

Discovery of new bioactive molecules for use in crop protection

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).

Discovery of new bioactive molecules for use in crop protection

Secondary Supervisor(s): Dr Lijiang Song (Chemistry)

University of Registration: University of Warwick

BBSRC Research Themes:

Sustainable Agriculture and Food (Plant and Crop Science)
Understanding the Rules of Life (Microbiology)

Project Outline

General background

Many of the bioactive molecules used in agriculture are made by microorganisms or inspired by natural products. For instance, abamectin derives from actinomycete bacteria and is one of the most widely used insecticides in crop protection. The Alberti lab aims to discover new bioactive natural products using a combination of genomics, genetic engineering and analytical chemistry, with the aim to improve the repertoire of molecules available for crop protection.^1–3

Project background

We previously isolated and characterised fungal strains of the genus Trichoderma that show inhibition of the growth of plant pathogenic bacteria.⁴We have identified candidate biosynthetic gene clusters within their genomes that we believe to be involved in the biosynthesis of novel bioactive molecules.

Aim and Objectives

Aim: to discover and characterise antimicrobial natural products from fungi that can be used in crop protection to fight plant diseases.

Objectives:

To clone and heterologously express the biosynthetic gene clusters of interest (Fig. 1A);
To isolate and characterise the corresponding natural products, including polyketides and non-ribosomal peptides (Fig. 1B);
To assess the bioactivity of the isolated compounds against a panel of plant pathogenic bacteria, including on plants, and to evaluate their cytotoxicity on human cells (Fig. 1C).

Methodology

Gene cloning, such as Golden Gate assembly, Gibson assembly and yeast-based homologous recombination will be used to clone the genes of interest and assemble them into suitable expression vectors for heterologous expression in Aspergillus oryzae;
Metabolite analyses will be performed through LC-MS and NMR spectroscopy (previous experience in these techniques is not essential) in order to characterise the pathway products and define the catalytic function of the relevant enzymes;
Antimicrobial bioassays will be performed against a panel of plant pathogenic bacteria, including on plants, to assess the bioactivity of the isolated compounds;
Genetic engineering will be performed (e.g. through CRISPR/Cas9) with the aim to study and improve the production of the molecules of interest.

Impact

This PhD project will lead to the development of biological control agents for plant disease, and will have long term impact on agricultural practices.

References

(1) Al-salihi, S. A. A.; Alberti, F. Genomic Based Analysis of the Biocontrol Species Trichoderma Harzianum: A Model Resource of Structurally Diverse Pharmaceuticals and Biopesticides. Journal of Fungi 2023, 9, 895.

(2) Brooks, S.; Weaver, J. A.; Klomchit, A.; Alharthi, S. A.; Onlamun, T.; Nurani, R.; Vong, T. K.; Alberti, F.; Greco, C. Unveiling the Potential of Daldinia Eschscholtzii MFLUCC 19-0629 through Bioactivity and Bioinformatics Studies for Enhanced Sustainable Agriculture Production. Frontiers in Chemical Biology 2024, 3, 1362147. https://doi.org/10.3389/fchbi.2024.1362147.

(3) Klomchit, A.; Calabon, M. S.; Worabandit, S.; Weaver, J. A.; Karima, E. M.; Alberti, F.; Greco, C.; Mahanil, S. Unveiling Novel Neocosmospora Species from Thai Mangroves as Potent Biocontrol Agents against Colletotrichum Species. J Appl Microbiol 2024, 135 (5), lxae114. https://doi.org/10.1093/jambio/lxae114.

(4) Tamizi, A.; Mat-amin, N.; Weaver, J. A.; Olumakaiye, R. T.; Akbar, M. A.; Jin, S.; Bunawan, H.; Alberti, F. Genome Sequencing and Analysis of Trichoderma (Hypocreaceae) Isolates Exhibiting Antagonistic Activity against the Papaya Dieback Pathogen, Erwinia Mallotivora. Journal of fungi 2022, 8, 246. https://doi.org/https://doi.org/10.3390/jof8030246.

Understanding the biosynthesis and mode of action of the anticancer antibiotic pleurotin for production of new analogues

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).

Understanding the biosynthesis and mode of action of the anticancer antibiotic pleurotin for production of new analogues

Secondary Supervisor(s): Dr Manuela Tosin, Dr Lona Alkhalaf

University of Registration: University of Warwick

BBSRC Research Themes: Understanding the Rules of Life (Microbiology, Structural Biology)

Project Outline

General background

Fungi are prolific producers of bioactive molecules used in medicine. For example, penicillin and cephalosporin antibiotics represent together 47% of the global antibiotic market. The Alberti lab aims to understand the biosynthesis of bioactive molecules, with the goal to direct it towards the production of new analogues.^1,2

Project background

Pleurotin is an anticancer antibiotic made by fungi that has potential to be an anticancer lead against breast and colon cancer. The Alberti lab recently used a combination of genome sequencing, comparative transcriptomics and isotope-labelled precursor feeding to study the early steps of pleurotin biosynthesis (Fig. 1).³

Aim and Objectives

Aim: to fully elucidate the biosynthesis of pleurotin and study its interaction with its target in human cells, in order to further develop new and improved pleurotin analogues.

Objectives:

To isolate and characterise pleurotin biosynthetic intermediates from engineered fungal strains;
To study the interaction of pleurotin with its target in human cells;
To produce new analogues of pleurotin using precursor-directed biosynthesis.

Methodology

Metabolite analyses will be performed through LC-MS and NMR spectroscopy in order to characterise the pathway products and define the catalytic function of the relevant enzymes (Fig. 1A);
Synthetic organic chemistry will be utilised to generate some precursors for feeding experiments.
X-ray crystallography will be used to investigate the interaction between pleurotin and its human target, thioredoxin reductase (Fig. 1B);
Precursor-directed biosynthesis, potentially in combination with gene knockouts through CRISPR/Cas9, will be used to produce new analogues of pleurotin with the aim to improve its bioactivity and pharmacokinetic properties (Fig. 1C). These will be purified using HPLC and tested for bioactivity.

Impact

This PhD project will increase our understanding of the biosynthesis of an anticancer lead and of its interaction with its molecular target, which will allow us to design more effective analogues.

References

(1) Alberti, F.; Khairudin, K.; Venegas, E. R.; Davies, J. A.; Hayes, P. M.; Willis, C. L.; Bailey, A. M.; Foster, G. D. Heterologous Expression Reveals the Biosynthesis of the Antibiotic Pleuromutilin and Generates Bioactive Semi-Synthetic Derivatives. Nat Commun 2017, 8 (1), 1831. https://doi.org/10.1038/s41467-017-01659-1.

(2) Alberti, F.; Khairudin, K.; Davies, J. A.; Sangmalee, S.; Willis, C. L.; Foster, G. D.; Bailey, A. M. Biosynthesis of Pleuromutilin Congeners Using an Aspergillus Oryzae Expression Platform. Chem Sci 2023, 14, 3826–3833. https://doi.org/10.1039/d2sc06638f.

(3) Weaver, J. A.; Alkhder, D.; Prasongpholchai, P.; Tadesse, M. D.; Santos, E. L. D. L.; Song, L.; Corre, C.; Alberti, F. Early Steps of the Biosynthesis of the Anticancer Antibiotic Pleurotin. bioRxiv 2024. https://doi.org/https://doi.org/10.1101/2024.08.27.609176.

Co-supervisor on projects with Professor Gary Bending and Dr Matthew Jenner.

Previous Projects (2024-25)

Primary supervisor for:

Harnessing biopharmaceuticals from microorganisms

Co-supervisor on a project with Professor Tim Bugg.

Previous Projects (2023-24)

Primary supervisor for:

Harnessing biopharmaceuticals from microorganisms