Prof Aoife McLysaght discusses her research in genetics and responding to Covid-19 through the Independent Scientific Advocacy Group.
At the start of her journey into a scientific career, Aoife McLysaght was looking at lab technician courses because those were the jobs in science that she was most aware of.
“I didn’t have any idea about research,” she said. “I suppose I hadn’t thought deeply enough to figure out who does the figuring out.”
However, she said giving herself permission to pursue an academic career and figure the rest out later was a great decision. “I never imagined that I’d still be university.”
While McLysaght has a few strings to her bow, her university role is professor of genetics at Trinity College Dublin and her research work focuses on evolutionary genomics.
“We are looking at genome sequences and trying to figure out patterns within them,” she said. “In some cases, there’s variations in the genome that affects survivorship and that’s where natural selection kicks in.”
There are two things she is specifically looking at in this space. The first is the origins of new genes and how they come to be. The second area is around gene and genome duplication, the latter of which would be all of the genetic material in an organism rather than a single gene.
“It might sound like a very fine difference between just duplicating genes one by one or duplicating them all in a block, but it turns out that it becomes a very important difference because some genes are generally not duplicable, which means if they get duplicated it tends to be negative, because it upsets the balance in the organism or in the cell.”
Disease and personalised medicine
McLysaght explained that because the balance of these genes’ components needs to be just right, they require a mass duplication to ensure the ratios remain the same. Any duplication that upsets the balance can lead to disease.
“It became this avenue into understanding various human disease genes as well and it was kind of by accident in the sense that we hadn’t set out to understand human disease genes, we’d set out to understand these evolutionary processes,” she said.
“But in thinking about them and interpreting them, it came out that this kind of evolutionary sensitivity that we’re seeing is still maintained now. So when you get a mutation that disrupts the amount of something, it’s one of the ways of having a disease outcome.”
‘If you can understand at a fundamental level the cause of the symptoms you’re seeing, then you can try and address the cause’
– AOIFE MCLYSAGHT
While McLysaght doesn’t work in the drug development side of things, she said this research has the potential to help address diseases caused by these gene mutations.
“You might recognise what’s missing, but it doesn’t mean it can be easily replaced,” she said. “[But] if you can understand at a fundamental level the cause of the symptoms you’re seeing, then you can try and address the cause.”
She also said this research can play a role in personalised medicine.
“If you imagine a process almost like a production line. If it breaks anywhere along the line, you get the same end effect, but it can be breaking at different points. So, you could have a medicine which addresses ‘here’ and it doesn’t help the individual who has a problem later on in the production,” she said.
“So understanding that sometimes people with similar symptoms actually have a different underlying cause, then you could give people directly the medicine that treated the thing they were lacking.”
Joining the fight against Covid-19
Outside of her work in genetics, McLysaght is a member of Ireland’s Independent Scientific Advocacy Group (ISAG), which was founded independent of the Government in June 2020 to discuss the science behind Covid-19 and response strategies.
She said the group was formed because she and the other members felt there was a “missing voice” in terms of discussing other ways of tackling the Covid-19 crisis.
“I think the biggest frustration was that the national strategy appeared to be quite short term. Thinking, ‘If we get through these two weeks, it’ll all be fine and then we can relax again’. And I think that has been the problem throughout.”
She said it has been an interesting experience because, while there aren’t many scientists and medics who disagree on the science around the virus, the disagreement comes at a political level. This can be a great source of frustration.
“[In ISAG], we have a lot of different expertise. Mathematical analysis, public health expertise, pandemic management, various kinds of analysis of genomics, all of these kinds of things. We learn a lot from each other and it has been a really interesting experience in terms of combining all that knowledge in a totally goal-orientated way.”
‘Recognising that this is a multi-disciplinary problem is actually important’
– AOIFE MCLYSAGHT
Another aspect of the pandemic McLysaght has found frustrating is around misinformation. There’s a huge amount of people “who are really confident” about certain things, even though they may not be true.
“I had somebody tell me: ‘Every virus evolves to be benign.’ But, no it doesn’t.” She said factoids like this one have become widely circulated even though there are numerous examples of viruses that never evolved to be benign, including HIV and measles.
“There’s a few individuals who I think are genuine bad actors, trying to push this kind of misinformation. And then there’s a lot of innocent people who are believing it.”
However, among all the frustrations, McLysaght agreed that there were some big wins for science when it came to the pandemic.
“I think a lot of people have learned a lot in terms of understanding the whole thing. Witnessing the vaccine development and roll-out in real time, that was pretty amazing. A lot of people do actually listen and have understood the modelling and the predictions,” she said.
“I think recognising that this is a multi-disciplinary problem is actually important, but it’s also interesting in terms of sparking interest in science as well and seeing how all of these different aspects are important.”
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