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Research Interests
Bacterial pathogenesis, virulence factors, molecular mechanisms of disease, mechanisms of ageing.
Understanding the molecular mechanisms of bacterial virulence factors
A common theme in bacterial pathogenesis is the secretion of bacterial virulence factors that can modify host cellular functions to evade host defense systems; these may be adhesion factors, invasions factors, endotoxins or exotoxins. To alter the host cell, bacterial virulence factors must reach their host target and the ability of bacterial proteins to gain access to the host cell cytoplasm is often a critical step in pathogenesis. In this aspect, processes such as type III, type IV and type VI secretion systems exist in pathogens. For example, the secretion of these virulence factors allow pathogens such as Salmonella Typhi to interact with host cells and create unique niches for replication and dissemination.
To understand the molecular mechanisms of these virulence factors we are using the well-studied model organism – Saccharomyces cerevisiae. The molecular biology of the single-celled budding yeast is well established and it is amenable to high-throughput systems. It also has a high degree of conservation of basic molecular and cellular mechanisms to human cells, making it a heterologous and cellular eukaryotic environment suitable for many fundamental studies.
We are currently studying virulence factors from Salmonella Typhi and Leptospira interrogans in this yeast system by using high-throughput cloning and protein expression systems followed by protein-protein interaction studies.
Molecular mechanisms of ageing in yeast
The quest for life span longevity has taken place throughout the ages in light of our mortality. Currently, certain genetic and proteomic basis of ageing has been identified across organisms from unicellular yeasts to multi-system higher organisms. Scientists have discovered that these evolutionarily conserved molecular pathways are universal and hint at an ancient origin of the biology of ageing. Despite advancements in the field of ageing research with the help of molecular biology, we have only begun to understand some of the mechanisms of these ageing-related molecules.
Ageing is a biological process involving many proteins and biochemical pathways. Molecular senescence leads to impaired biochemical pathways that affect organismal ageing and lifespan in all organisms. In yeast, the chronological life span (CLS) is the measurement of the survival time of a population of non-dividing yeast cells during the stationary phase.
Researchers have shown that dietary change such as calorie restriction can improve health and life span. This project investigates intracellular (proteins) and extracellular factors (natural compounds) that affect cellular lifespan using a yeast CLS assay. It is hypothesised that these factors can extend lifespan or delay ageing by modulating the molecular mechanisms of ageing-related pathways in yeast. Such insights will aid our further understanding of the ageing process.
Production of recombinant antigenic proteins as diagnostic biomarkers
Antigenic proteins can act as diagnostic biomarkers for the detection of diseases through serology and antibody assays. Our group has established the capacity to produce and purify recombinant antigenic proteins for the detection of Salmonella Typhi acute and carrier individuals.
We first produced recombinant antigens and performed an enzyme-linked immunosorbent assay (ELISA) screen to detect the presence of potential typhoid carriers amongst asymptomatic food handlers (Franklin et al, 2020, doi:10.1007/s00430-020-00667-1). We found the presence of antibodies against the carrier biomarker (YncE) in several food handlers's serum. These suspected carrier individuals may cause a typhoid outbreak if they accidentally contaminate the food during preparation and they do not observe hygiene measures.
As an extension of our research, we also provide gene cloning, recombinant protein expression and purification, and other research services.
For enquiries, please email: eugene@usm.my
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