‘Errors in cell division can promote adaptation to a new environment in an organism,’ says Dr Mihailo Mirkovic.
The University of Galway has tapped biochemistry expert Dr Mihailo Mirkovic to lead a new research program investigating the impact of cellular stress and disruption of RNA processing in fungi, in the hope of better preventing chromosome abnormalities that can lead to cancer and neurodegenerative disease.
Mirkovic joins the center on a Wellcome Trust award, and will establish a group within the University’s Center for Chromosome Biology.
Originally from Montenegro, Mirkovic completed his bachelor’s and master’s degrees at the University of Belgrade in Serbia, before moving to Portugal for his PhD studies at the Instituto Gulbenkian de Ciencia and ETH Zurich, for his postdoctoral research.
“My PhD work focused on cell division,” Mirkovic said, describing his work.
“During every cell division, the DNA in the cell must be replicated, spliced together and precisely divided into two daughter cells.
“I worked on the mechanisms of how cells keep their DNA copies together and how they separate over time.
“We discovered that errors in keeping the duplicated DNA cells together are not properly recognized by the dividing cell, and lead to developmental disabilities, especially in the brain.
“We found that old yeast cells have problems dividing their DNA accurately.” We discovered that this is because old yeast cannot process its RNA properly and stores it in the cell nucleus until it is properly processed.
“This condition changes the function of the genes and results in uneven DNA replication in old age, followed by cell death. When we used a few genetic strategies to prevent this RNA processing disorder, cells improved their DNA replication in old age and lived longer.”
Tell us about the research you are currently working on.
The topic of cell division and uneven DNA division is of great interest to the general public, as it affects human health and development. However, it has another interesting twist, and that is that errors in cell division can promote new adaptations in an organism.
Equal DNA partition produces identical DNA information in two cells. Unbalanced DNA replication creates cells with different, “new” genetic information. These new cells can adapt to the different challenges they face.
For example, fungi use unequal DNA fragmentation to resist stress, including clinically used antifungal drugs. Since errors in cell division are essential for fungi to survive stress, I want to test whether these organisms have a way of making these errors “on purpose” in order to survive.
This is quite the opposite, as errors in DNA replication are costly, and often cause many problems for the cell. But in situations of death, when faced with stress, these mistakes seem more desirable than stopping and continuing with the same old genetic information. This process can influence how cells develop antimicrobial resistance (AMR) which is a pressing public health problem.
In your opinion, why is your research important?
It aims to reveal more about a potentially very interesting phenomenon from the aspect of basic science and to understand cell division in times of stress.
If we find something interesting there, we will try it on pathological types of fungi. This can help us understand how they adapt to antifungal therapy in settings that may be relevant to human health in the future. But this is not a given.
The most important thing to note, is that it is very difficult to measure the impact of research as it happens. Research that directly benefits public health is the very pyramid of knowledge and application.
For these clinical discoveries to happen, hundreds of basic science research projects had to be carried out, using anything from bacteria to worms to mice as model systems. This collection of information was necessary to even start working on problems related to people’s health.
In order to have a strong apex in terms of application and impact, the foundation, from which all primary knowledge is generated, which we call basic science, must be healthy.
What inspired you to become a researcher?
I have always loved looking at nature, but also browsing rocks, looking, holding and learning about different living things as long as I know them.
(Un)luckily, like many people who dream of becoming a marine biologist or zoologist, I ended up in a lab of some sort. What saves me in the lab is microscopy. The ability to observe cells directly and watch them do things still sparks the same spark of observation.
My PhD supervisor took me to the microscope to show me how a cell divides on my first day of work. After that I was bet.
What are some of the biggest challenges or misconceptions you face as a researcher in your field?
Great scientific challenges are found in all fields. It’s a dangerous job where only a small percentage of people who start their doctorates end up running their own research programs.
People are constantly applying for limited funding in all categories, and it is very difficult. This type of pressure leads people to try to justify or market their science with promises of direct “impact”, which is easy to explain to the taxpayer or funding agency.
I think that in this situation we all lose, if not in the quality of the science being supported, then at least in honesty and teaching the public how scientific progress really works.
I was very fortunate to do my PhD and postdoc in labs and institutions where the importance of basic research is recognized both academically and with adequate research funding. Some of our colleagues are less fortunate.
Do you think the public’s interaction with science and data has changed in recent years?
I think communication of science and society has always been lazy, Covid has just brought it to the fore.
Laziness on two sides, scientists find it beneath them (or don’t know how) to simplify their research topic even when talking to other scientists, let alone a member of the public.
On the other hand, journalists looking for headlines like “researcher X cures cancer”, are specially nurtured and rewarded in the modern struggle for clicks and engagement.
Covid is a tricky example, like telling people that our knowledge of a problem is evolving, and that things we say a month ago may not be true the next month, they may be scientifically accurate and reliable, but it would be a bad public health communication strategy, I’m not sure I know enough about the balance of these two things to comment.
The former director of the National Institutes of Health, Francis Collins, admitted that the failure to explain the developing science is one of the important reasons for the loss of public trust.
What I do know is that no one likes to be talked down to, and very few people will be moved to good action if they are told that they are ignorant and stupid.
It is the duty of science communicators not to preach to the converted, but to try to reach those who had little knowledge of science at school or in everyday life and to fight the spread of inaccurate information.
It is the duty of governments and schools to introduce rigorous, engaging and interactive science courses in schools to ensure that the public has a basic understanding of how knowledge is obtained, and what is real and what is not.
How do you encourage engagement in your personal work?
Well, I am writing these lines…
On a more serious note, as a postdoc or PhD student you are less likely to make effective scientific connections beyond your immediate social circle.
During my PhD, there was a music festival in Lisbon, and our institution hired a bunch of PhD students to go around and talk to the festival attendees about anything science-related they might be interested in.
That was an amazing experience, as people are actually curious when they are given the opportunity to participate and when they are approached in the right way. For me it was perfect, as I drank beer and chatted, two things I am very good at. Now that I have my own research group, I will explore different options to engage with the University of Galway in the local community.
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