Marina Ezcurra received her PhD from the Karolinska Institute in 2011. Her PhD research was a collaborative project between Karolinska and MRC-LMB, Cambridge, and she studied neural circuits and behavior using C. elegans in Bill Schafer’s group. During her PhD, Marina Ezcurra identified extrasynaptic mechanisms by which nutritional status modulates nociception, involving neuropeptidergic and dopaminergic signaling. She went on to do a postdoc working on ageing with David Gems at University College London. During her postdoc, Marina Ezcurra developed methods to monitor the development of multiple age-related diseases in vivo in C. elegans, leading to the discovery of a previously unknown process, Intestinal Biomass Conversion. This mechanism enables the C. elegans intestine to be broken down to produce vast amounts of yolk, resulting in polymorbidity and mortality in ageing nematodes. This work illustrates how ageing and age-related diseases can be the result of run-on of wildtype gene function rather than stochastic molecular damage. Current research in Marina Ezcurra’s group focuses on how host-microbiome interactions affect host ageing and is funded by The Wellcome Trust and Royal Society. Marina Ezcurra is a trustee board members of The British Society of Research on Ageing.
ORCID ID: 0000-0003-2739-6984
For full information Marina's work, visit her research website: marinaezcurralab.com
Genomic approaches are greatly advancing our knowledge of the human microbiome and its role in health and disease states. It is becoming clear that the composition of the microbiota varies greatly between individuals, contributes to many diseases and plays an active role in human health. A number of recent studies have shown that the gut microbiota modulates important aspects of human physiology, including the ageing process and the myriad of associated diseases, and also the gut-brain-axis, resulting in effects on neural chemistry, behaviours, psychiatric and neurodegenerative diseases. Thus, the microbiota presents an avenue to target novel treatments to a number of diseases and to modulate brain plasticity and cognitive function during ageing.
Due to the inherent complexity and heterogeneity of the human microbiome this complex relationship between the host and its microbiota is very difficult to disentangle in mammalian systems. We are using the nematode C. elegans combined with its native microbiome but also with bacterial models to identify the microbial and host pathways underlying microbiome effects on the gut-brain axis during ageing. On one side, the combination of C. elegans with bacterial models offers exceptional experimental systems allowing the systematic manipulation of the host and its microbiota, and the use of all the tools these models offer to gain mechanistic insight into microbiome effects on host physiology. On the other side, studying C. elegans with its native microbiome allows the study of ecologically relevant host-symbiont interactions.
MSc-R project available for September 2021
Using microbiome-based compounds to develop new therapeutics (MSc by Research in Microbiology)
Jointly supervised with Dr Simon Moore
Host-microbiome interactions have been associated with a wide range of diseases, including inflammatory bowel disease, cancer, depression and neurodegenerative diseases. An important biological challenge is to determine the molecular mechanisms underlying these effects and use them to improve host health. In this project we will use a laboratory host-microbiome model system – the nematode C. elegans combined with a defined experimental microbiome – to identify microbial compounds that improve host health. The project involves synthesising and purifying candidate compounds in the Moore lab and validating their effects in the C. elegans model in the Ezcurra lab. Our goal is to develop innovative approaches to microbiome-based therapeutics. Therapies based on compounds from the microbiome have massive potential as manipulating the microbiome through probiotics or faecal transplants presents problems in achieving predictable outcomes on microbial communities and host health.
Novel model systems to monitor biofilm formation in Pseudomonas aeruginosa chronic infections (MSc by Research Microbiology)
Jointly supervised with Dr Becky Hall
Pseudomonas aeruginosa is a re-emerging, multidrug-resistant, opportunistic pathogen that causes life-threatening chronic infections. The major characteristic of chronic P. aeruginosa infections is the formation of biofilms, in which the cells are surrounded by exopolysaccharides and form structured aggregates. P. aeruginosa biofilms exhibit increased resistance to antibiotics and host immunity, making these infections almost impossible to eradicate. Novel therapeutic strategies aimed at biofilms are therefore urgently needed.
Currently, standardised microbiological assays of Pseudomonas aeruginosa do not take into account the role that biofilms play in pathogenicity and antibiotic resistance. They are often performed in vitro, in the absence of host immune responses. The aim of this project is to develop a new model system to enable monitoring of Pseudomonas aeruginosa biofilms in real time in a whole animal using the model organism C. elegans as a host. This will enable screening for antimicrobial interventions that specifically target P. aeruginosa biofilms in vivo as means to treat chronic infections.