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 2020
Live strong and healthy – Understanding the links between the microbiome, muscle function and healthy ageing - joint supervision with Professor Dan Mulvihill
The disastrous consequences of the ongoing COVID-19 pandemic highlights the importance of healthy ageing for wider society. Frailty is a major risk factor for ill-health in old age and is the result of changes such as muscle weakness, immune dysfunction and chronic inflammation, leading to reduced physiological functions and increased vulnerability to infections. In this project we will investigate how the microbiome can be used to maintain muscle function and motility in late life, and determine links between muscle function, immunity and age-related health. We will dissect molecular mechanisms underlying microbiome effects on frailty, muscle function and immunity using the model organism C. elegans to perform behavioural and physiological studies in vivo, complemented with in vitro and biochemical approaches. Our aim is to establish evolutionary conserved host-microbiome interactions that can be utilised to support healthy ageing in humans.
Additional research costs: £1500
Effects of host-microbiome interactions on the ageing nervous system The composition of the microbiome plays an important role in human physiology, with microbial diversity being associated with health, and decreased diversity associated with ageing and ill-health. Studies in humans have shown links between microbiome composition and neurodegenerative diseases such as Parkinson’s and Alzheimer’s disease, suggesting that the microbiome contributes to these diseases and perhaps the ageing process itself. Due to the large degree of complexity of the mammalian microbiome, causation has not yet been established and mechanisms underlying host-microbiome effects on health remain unknown. There is a strong need to establish simple, genetically tractable models allowing the untangling of these complex interactions.
Our group uses the model organism C. elegans to dissect the mechanisms underlying host-microbiome interactions and their effects on host health, with a focus on the ageing nervous system. We have shown that the microbiome has strong effects on disease progression in C. elegans models of Parkinson’s and Alzheimer’s disease. This project will involve screening probiotic strains for effects on neurodegenerative disease models with the aim to identify strains that improve late-life health. The underlying processes, including host-microbiome interactions affecting innate immunity, mitochondrial biology, protein homeostasis and stress responses, will be investigated. The nature of the relevant microbial signalling pathways will be investigated through biochemical and genetic approaches.
The project will involve developing skills in modern neuroscience, genetics, bioinformatics, biochemistry, microbiology, and microscopy. Additional research costs: £1500