School of Molecular Biosciences

“Breaks and Crosses - Insights into the molecular mechanisms of meiotic recombination”

What makes us unique? At the cellular level, our genetic diversity is a key element of our individuality, reflecting a unique mix of traits inherited from our parents. To generate viable haploid gametes, the genome must be halved through a specialised form of cell division; meiosis. During meiosis I, homologous chromosomes must be accurately segregated, which first requires their physical linkage. But how do homologous chromosomes pair and become connected? In most organisms, this is achieved through homologous recombination, which repairs programmed DNA double-strand breaks in a biased manner to generate crossovers. How is DNA break formation regulated? And how is the repair machinery directed to favour crossover outcomes? In this talk, I will present our ongoing work using biochemical reconstitution to dissect the molecular mechanisms that underpin meiosis I. In part one, I will discuss the proteins that assemble on meiotic chromatin and how they recruit and activate the break-forming machinery. In part two, I will explore how DNA repair intermediates are stabilised to become mature crossovers. Our findings illuminate not only fundamental aspects of cell biology but also the potential roles of germline-specific factors in the development of somatic cancers.

“Regulation of plant greoeth by the SNRK1 Signalling"

Plant growth and development are largely influenced by environmental conditions. An increasing body of evidence suggests that environmental information is partly conveyed as sugar signals which have accordingly been linked to stress responses, phase transitions such as germination and flowering, and growth control. A central component of the sugar signalling network is the evolutionarily conserved AMPK/SnRK1 protein kinase. SnRK1 is activated under low carbon conditions often associated with stress, driving a vast metabolic and transcriptional reprogramming that promotes energy-saving and nutrient remobilization strategies.

In this talk, I will show that several aspects of plant growth and development are regulated by the SnRK1 signalling pathway in response to sugar availability but also in response to the phytohormone abscisic acid that signals water scarcity. I will also discuss our progress on the mechanisms by which SnRK1 is regulated by sugar signals, enabling the coordination of metabolism and growth with sucrose supply.

"Targeting extracellular proteases to develop antibiofilm peptides”

Biog: Dr Czekster is a Brazilian biochemist and Reader at the University of St Andrews. Her interdisciplinary research focuses on pathogenic bacteria and the development of strategies to combat infectious diseases. Dr. Czekster began her academic training at the Federal University of Rio Grande do Sul (UFRGS), earning a BSc in Molecular Biology and a teaching degree in Biological Sciences, followed by an MSc in Biochemistry, where she investigated enzymes involved in tryptophan biosynthesis. She completed her PhD at the Albert Einstein College of Medicine, specializing in enzymes related to tetrahydrofolate biosynthesis in Mycobacterium tuberculosis. Her postdoctoral work at Yale University expanded her focus to include beta-amino acids, aminoacyl-tRNA synthetases, and their incorporation in nascent proteins by modified ribosomes. In 2015, she joined the University of St Andrews as a postdoctoral researcher in Prof. Jim Naismith’s group, examining the biosynthesis of fungal and plant cyclic peptides including amanitins and segetalins. In 2017, Dr. Czekster became an independent research fellow, and in 2018, she was awarded a prestigious Sir Henry Dale Fellowship from the Wellcome Trust, enabling the establishment of her independent research group in the University of St Andrews. She runs a citizen science project “Antibiotics under our feet” to engage with learning settings and better understand microbes. In 2025 she was one of the winners of the ACS Infectious Diseases Young Investigator Award for her work in chemical biology and infectious diseases.

"Protein persulfidation enters a new phase" 

To sustain life, nature relies on a limited set of chemical reactions; among them is sulfur-based chemistry, which primarily controls intracellular redox homeostasis and redox signalling. Hydrogen sulfide (H2S), one of the simplest sulfur-containing molecules in cells, has attracted significant attention since its potential physiological roles were first proposed. One of the main mechanisms by which H2S signals is the post-translational modification of cysteine residues, known as persulfidation. Key questions remain about how protein persulfides form in cells and how they affect cellular function, particularly in the context of aging and age-related diseases. This talk will examine structural versus functional effects and controlled versus stochastic formation of persulfides. Specifically, I will introduce liquid–liquid phase separation—a mechanism by which cytoplasmic components (proteins and RNAs) assemble into distinct, membraneless compartments (biomolecular condensates)—as a primary way through which H2S-induced protein persulfidation regulates cellular function and could be used to improve health- and lifespan.

“Secretion of antibacterial toxins by the Staphylococcus aureus type VII secretion system"

The Type VII protein secretion system (T7SS) is found in mycobacteria and in many Gram-positive bacteria including the human pathogen Staphylococcus aureus. S. aureus encodes a single T7SS that is genetically diverse between strains. The S. aureus T7SS machinery is composed of four membrane proteins, EsaA, EssA, EssB and EssC, and two additional globular proteins EsxA and EsaB. Structural studies and comparison with the mycobacterial T7SS suggest that EssC, a member of the AAA+ ATPase superfamily, protein most likely forms the secretion pore. Some strains of S. aureus secrete a large nuclease toxin, EsaD, through the T7SS that is very potent, and highly active against chromosomal DNA. S. aureus protects itself from the action of the nuclease by producing an anti-toxin that binds tightly to the nuclease, blocking its activity. The nuclease also interacts with a specific chaperone that appears to target the nuclease-anti-toxin complex to the secretion machinery. During secretion by the T7SS, the anti-toxin is probably dissociated from the nuclease and remains inside the cell while the nuclease is secreted. Co-culture experiments indicates that the T7-dependent nuclease mediates competition between closely related S. aureus strains, which is likely to be important during colonization. Recently we have characterised the T7SS-secreted toxin EsxX showing that it is a membrane-depolarising toxin with a glycine zipper motif. EsxX is profoundly toxic to bacteria, displaying toxicity from both cytoplasmic and extracellular compartments. A pair of polytopic membrane proteins, ExiCD, protect cells from intoxication by extracellular EsxX. By contrast, a distinct soluble heterodimer, ExiAB, neutralises cytoplasmic EsxX by sequestration of its glycine zipper motif in a binding groove on ExiB. Our work defines a new class of antibacterial toxin requiring two distinct types of immunity protein which follow different phylogenetic distributions.

The nucleus as a dynamic metabolic compartment linking nutrients to gene regulation"

We investigate the precise mechanisms by which dietary nutrients influence cellular and organ function, focusing on the role of metabolites as intracellular signalling molecules. We have recently developed rigorous approaches for subcellular metabolite analysis by liquid chromatography–mass spectrometry (LC–MS), with particular emphasis on acyl-Coenzyme A thioesters (acyl-CoAs).

Our work shows that the nucleus functions as a distinct metabolic compartment, mediating the dynamic relationship between nutrient availability and histone modification. Within the nucleus, metabolites act as substrates, inhibitors, and cofactors for chromatin-modifying enzymes, thereby contributing to the establishment and maintenance of gene expression and cell identity.

Our current research addresses three fundamental questions in nuclear metabolism:

1. What mechanisms support differential metabolism within the nucleus?
2. How does nuclear metabolism influence epigenetic regulation?
3. How do these processes affect physiological responses to dietary nutrients?

In this talk, I will highlight our recent findings on how propionate, a major gut microbiota–derived short-chain fatty acid, shapes hepatocyte function through nuclear propionyl-CoA generation and the emerging chromatin modification, histone lysine propionylation (Kpr). Our results point to a potential role for transient ‘epigenetic’ marks in shaping how the liver responds to nutrient cues.

“Visualizing Dynamic Regulation of the Ubiquitin-Proteasome System in Response to Signals”

The ubiquitin system is governed by the transient assembly of conformationally dynamic complexes. We are fascinated by how these molecular machines form and function in response to stimuli ranging from endogenous signals to degrader drugs mediating targeted protein degradation. We employ an integrated multidisciplinary approach to investigate crosstalk between cellular perturbations and the ubiquitin system—ranging from the development of chemical biology probes and proteomic profiling techniques, to biochemical reconstitution and high-resolution structures by cryo-EM, to in situ visualization of assemblies using cryo-electron tomography. We then aim to reconstitute these systems to uncover the underlying biochemical and high-resolution structural mechanisms. In this talk, I will present our latest findings on the visualization of dynamic assemblies involved in ubiquitin-mediated regulation.

"Nanoscale materials for control of mesenchymal stromal cell phenotype and development of blood cancer models"

After a PhD at Queen Mary University of London on osteoblast response to bioactive composites I moved to Glasgow to study cell-nanoscale interactions. In 2003 I became an independent researcher securing a BBSRC David Phillips Fellowship to explore mesenchymal stem cell response to nanotopography. Appointed to a lectureship in 2008 and a Readership in 2010, I became Professor of Cell Engineering at the University of Glasgow in 2014. I am currently co-Director of the Centre for the Cellular Microenvironment (https://glasgow.thecemi.org). I direct the EPSRC programme grant StemNiche looking at bioengineering stem cell niches for Pharma use and I direct an EPSRC research and partnership hub for health technologies, MAINSTREAM (https://www.mainstream-hub.org), on stem cell manufacturing. I also lead an EPSRC project grant on nanovibrational chondrogenesis, co-I on an EPSRC HT50 programme grant on prediction of blood cancer, am involved in an EPSRC large project led from QMUL looking at on-chip technologies and an EU H2020 grant focussing on GMP manufacture of cells and materials. In terms of translation, we have performed a number of veterinary trials for bone regeneration, most notably Eva the dog, but also 10 other cats and dogs. We are also working towards spin out of nanovibrational bioreactor technology and, against all odds, a human clinical trial of nanovibrated stem cell therapy. Further, I am Director of the EPSRC-SFI lifETIME centre for doctoral training (https://lifetime-cdt.org) that will train more than 80 PhD students in the UK and Ireland with science and leadership skills in non-animal technologies for Phrama drug discovery and regenerative medicine. In 2016 I was elected a Fellow of the Royal Society of Edinburgh and have won a number of awards – most recently the Biochemical Society Industrial-Academic Collaboration Award in 2020.

My interest now lies in understanding mesenchymal stem cell ageing in order to allow manufacture of large numbers of high quality stem cells for regenerative therapies, transplant therapies and deign of bioengineered drug screening models. In terms of models, I am interested in models of the bone marrow to study blood cancers. Blood cancer is an area where animal models give poor prediction and so human cell containing models are increasingly important, especially with the new stances of the MHRA and FDA, which are increasingly permissive to non-animal technologies. I will chat about these technologies in the seminar.

Enabling targeted protein degradation in bacteria

Are aquaporins expressed in stomatal complexes promising targets to enhance stomatal dynamics?

Probing the potential of the plant cell wall to act as a protective barrier against winter temperatures

Making Marvellous Molecules (and finding out what they do)

RETuning the electron transport chain in obesity improves metabolism

The Persulfide and Polysulfide Puzzle: Novel Tools and Methods to Assemble the Pieces

Breaks and Crosses - Insights into the molecular mechanisms of meiotic recombination