When his nephews were diagnosed with a rare neurological disease, Dr Lee Coffey pivoted his research to work on developing treatments.
Though he may be modest about his research achievements, Dr Lee Coffey’s work on gene therapies is hugely impactful, including for his own family.
Coffey is a lecturer and researcher in molecular biology with biopharmaceutical science in the Department of Science at South East Technological University (SETU) and a principal investigator at the Pharmaceutical and Molecular Biology Research Centre (PMBRC). He has also set up and leads a SETU spin-out called BioEnz Technologies.
“I was always particularly fascinated with how DNA – a biological code for you, your life and body, and a significant aspect of your personality and moods – is written and resides in our cells,” Coffey tells SiliconRepublic.com.
“The subtle changes and profound effects from variations in this code (or its expression) are just incredible – I think this comes from being an identical twin, where the sequence we were given said that we would be identical, but we are ever so slightly different physically and in terms of behaviour.”
Coffey completed a BSc in applied biology and a PhD in molecular biotechnology, both at Waterford Institute of Technology. As a postdoctoral researcher, he established international collaborations and worked in the UK and South Africa.
He has been lecturing full time for 13 years, with a packed lecturing schedule each week – “so research really is something that you squeeze in between all the undergraduate prep and delivery,” he says.
His diverse research, which has included enzyme discovery for biofuels, developing biological sensors for disease detection and building synchronised bacterial systems to treat mastitis, has always focused on tangible applications, he says.
“No research output is possible without the postgraduate and postdoctoral researchers involved, and sometimes the real research ambition is (or should be) to provide starting or early-career researchers with the same opportunities that myself and others were already given.”
Tell us about your current research.
The gene therapy research that we are carrying out now is focused on developing an enhanced gene therapy for a particular rare neurodegenerative disorder called Canavan disease.
Some years ago, my identical twin brother was told that both of his sons, an infant and a two-year-old at the time, had Canavan disease. There were treatments and gene therapy solutions being developed but nothing on the market, so I absolutely had to contribute to the research area somehow.
‘I absolutely had to contribute to the research area somehow’
I established a collaboration with world-renowned researchers in the field of gene therapy and Canavan disease research, Dr Guangping Gao and Dr Dominic Gessler from UMass Chan Medical School. These internationally recognised gene therapy researchers had already developed Adeno-associated viral (AAV) delivery vectors and had gene therapy solutions under study, but I wanted to apply my experience of gene evolution and enzyme enhancement to contribute if possible.
Canavan disease is caused by accumulation of N-acetyl aspartate (NAA) in the brain, due to the deficiency of aspartoacylase (ASPA) enzyme, associated with mutations in the ASPA gene.
Gene therapy solutions being developed focus on delivering the ASPA gene past the blood-brain barrier and therefore enabling healthy ASPA enzyme production.
The collaborative research that we have been doing in SETU focuses on generating thousands of evolved variants of the ASPA gene and enzyme, searching for an enhanced or ‘super’ ASPA. High performing candidates are then combined with the UMASS AAV delivery system to undergo disease model trials.
This work has taken shape as a PhD project, now completed, and a European Leukodystrophy Association (ELA International) funded postdoctoral research project, the first time a project in Ireland has been funded by this agency.
The work in SETU has moved to a second generation of evolved, high-performing ASPA candidates, combining random and focused gene evolution techniques. We hope to again trial these in UMASS with disease models later in the project.
The postgraduate and now postdoctoral researcher working on this in SETU, Dr Sarah Foley, has worked incredibly hard to get the work to this stage.
In your opinion, why is your research important?
I don’t know if my two nephews, who are now 8 and 10 years old, will ever benefit from this research but future Canavan disease sufferers should benefit at least.
If an enhanced gene therapy reaches the market, a single dose should give more efficacy or benefit to the patient. A higher efficacy can also mean that a lower dose may be given to a patient, reducing the risk of side effects, and also costs (another major barrier for gene therapies in general).
Outside of my own hopes and fears, and Canavan disease, the approach we have taken has not been done before in terms of gene therapy enhancement. This work could serve as a model to other researchers to apply and enhance gene therapies for a range of other diseases.
What inspired you to become a researcher?
I was always fascinated by biology and life on this planet, and I think most people are – nearly everyone loves nature programmes like David Attenborough’s.
I was lucky to have inspiring biology teachers in school and then lecturers in university. I loved the nature of research from the start of my career – there is a challenge in recognising something unsolved or that could work better, or could be built; be it the cause of a disease or its cure, or even just an enzyme that might work better in a process somehow.
Coming up with a problem-solving path or plan to meet that challenge is really enjoyable, and your day is never the same.
Science needs a technical and logical approach but good research needs innovative and creative thinking also – getting these mindsets or ways of thinking to work together can be really rewarding.
What are some of the biggest challenges or misconceptions you face as a researcher in your field?
The biggest challenge absolutely has to be the lack of funding, and the need to pitch or apply for the next funding call in your spare time, to keep research going or to get it started.
Carrying out internal work in my own biotechnology company at times has spoiled me also – I can order a lab consumable online and receive it the next day.
In a university research lab with public procurement procedures, that click of a button takes a lot longer, which is unavoidable but can really limit research experiments.
‘The biggest challenge absolutely has to be the lack of funding’
The only real misconceptions I see in my area of work is from non-scientists and their view of GMOs and GM foods. I try to convince them in a five-minute pitch, but it is often a lost cause!
One challenge I do see, not for myself but for the next generation of scientists, is gender based.
Science was traditionally male-dominated, and in more recent years there has been a most welcome push to encourage women in science. In my exposure to laboratory science students nowadays, male students (and researchers) are in the vast minority and there are less opportunities in lab sciences for males, in funding calls, entrepreneurship drives etc.
I think that young males looking to start a career in lab or life science now face a bigger challenge, but hopefully this will change in the future and we will achieve equality for all in terms of support and opportunities, regardless of gender.
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