An interview with Dr Tim Regan

October 2020

Dr Tim Regan is a postdoctoral researcher based at the Roslin Institute at the University of Edinburgh, UK, and a member of the Microbiology Society. In this interview, he tells us more about his research into early-life host-microbiota interactions, why the relationship between pathogens and their hosts is important, and more about his research into CRISPR-Cas.

Tim Regan
© Tim Regan

Tell us more about your role and area of research.

I am a postdoctoral researcher in Dr Tim Bean’s group, which studies bivalve health at the Roslin Institute, University of Edinburgh. This involves drawing on my molecular biology, metagenomics, and immunology expertise. My main project uses genome sequencing to identify microbes associated with developing oyster larvae and their environment in a commercial oyster hatchery. By correlating community structure with metadata on the performance of these larvae over time, we aim to better understand which microbes – healthy or unhealthy – larvae should have, and how we may manipulate the microbial ecology to prevent disease development and increase overall performance.

Why is your research important?

I am particularly interested in early-life host-microbiota interactions and disease challenges in aquaculture. How the microbial ecological landscape evolves during this time can be crucial for the healthy development of the host. Perturbations in environmental stressors and diet can have significant effects on these communities which can last into adulthood. As we advance our understanding of these host-microbiota relationships, we discover ways in which these communities increase the health of the organism by improving its metabolism and disease resistance. I see enormous potential in harnessing these communities to increase the production, sustainability and welfare of aquaculture species.

Through studying and improving bivalve health, the applied research in our group improves food security and sustainability by reducing oyster hatchery mortalities. Additionally, however, oysters are also a keystone species and improve biodiversity and ecosystem restoration. Finally, following the ‘One Health’ ethos, a better understanding of basic invertebrate host-microbiota interactions can generally be applied to higher-order organisms.

Why should we take the time to study the relationship between pathogens and their hosts?

Microbes are everywhere, and their activity can have significant effects on macroecology. Pathogens, or disease-causing microbes, can cause disease or even mortality in their hosts. Understanding the relationship between pathogens and their hosts on an individual level helps us to better treat illness and reduce mortalities in humans and livestock. At a population level, this knowledge has huge implications not only for epidemiology and controlling the spread of disease, but also ecological protection and food security.

What did your research with CRISPR/Cas9 involve? How is it significant for treatment and prevention of disease?

These projects were coordinated by three different University of Edinburgh PI’s: Dr Finn Grey, Dr Kenny Baillie, and Dr David Dockrell. We employed disruptive mutagenesis screening with CRISPR/Cas9 to disrupt, or switch off every gene in the genomes of either pig or human cells in vitro (GeCKO screening). These edited cells were subsequently infected with a pathogenic microbe, in this case either influenza virus or the bacteria Streptococcus pneumonia, which cause flu, pneumonia, meningitis, or sepsis.

The infection level of the cells, or the cells' response to infection was analysed using fluorescence-activated cell sorting (FACS). The cells were then sorted into groups based on these measurements, allowing us to identify which genes were switched off in each group of cells through amplicon sequencing.

This way we could compare which host genes were involved in response to a pathogenic infection; i.e. which genes does the flu virus need to replicate within its host? Which of these genes across hosts? Which genes are required to mount a response against S. pneumonia? Answers to these questions can help direct therapies, to cure or prevent diseases such as flu, pneumonia and sepsis.

What are your thoughts on the current novel coronavirus outbreak? What does it tell us about pathogen and human interaction?

COVID-19 has already proven to be a devastating disease, having claimed many lives so far. However, it’s encouraging to see the conversations among the clinicians, epidemiologists, and evolutionary microbiologists on social media.

We live in a time where more information and data is shared than was previously ever imaginable. It was over a century ago when the last big flu epidemic occurred, therefore it’s wonderful to see the research community come together and use open science and modern technologies applied to this problem – including openly available published real time genomes for the virus as it spreads. This allows us to track its evolution and understand how it's spreading from person to person (You can learn more by visiting Professor Rambaut, University of Edinburgh's Twitter). 

This current outbreak also highlights the importance of researching host-pathogen interactions in other species, to monitor the myriad animal reservoirs for disease. Understanding these interactions is crucial for our management of these diseases where zoonosis occurs, and understanding the evolutionary processes involved during host species switching in the first place.

Finally, it is worth mentioning that this outbreak is raising awareness of pneumonia – an often easily treatable disease which kills more children than malaria, HIV and tetanus combined.

What kind of challenges do you encounter in your work and how do you overcome them?

A big challenge can be juggling multiple projects at a time. This, however, can have its advantages though, as a lot of the work I do has extended (and sometimes unforeseen) periods of down time, which allows me to focus on other projects. It is also very nice for maintaining sanity; when you hit a brick wall on one project, to have another thing to work on while you think through the stumbling blocks of the other, without getting too frustrated.

Why is it important to be a member of an organization like the Microbiology Society?

Science is all about collaboration and communicating research findings. As a research community, the Microbiology Society facilitates this through special interest group meetings and the annual conference, in addition to the publications, newsletters and the Society's website. Beyond encouraging collaborative research and supporting young researchers through these platforms and funding, it also brings members together to enjoy a shared passion for their research interests with one another.

Why does microbiology matter?

While often invisible to the naked eye, microbes are everywhere. Underlying and overlaying every habitat and surface, shaping the larger ecology through interactions which we increasingly continue to uncover and harness.

If you are a member of the Society and would like to find out more about how you can get involved with Society activities and/or showcase your research, please email us at [email protected].