Yolanda Markaki is a group leader and microscopist based at the University of Leicester, UK. Her lab, set up in 2023, focuses on the mechanisms of X chromosome inactivation. She is also passionate about gender equality in science.

Thank you for joining me! Can you please tell me a bit about what you are working on?

Yes! My lab focuses on how heterochromatin, the silenced genome, forms in early development. In particular, we are looking at the process of inactivation of one of the two X chromosomes in females. This takes place very early in life to ensure female cells have the same dosage of X-encoded proteins as males (they have only one X chromosome).

During my postdoc, I discovered that this process of switching off the X is conducted by molecular nanosized assemblies called SMACs. You need super-resolution microscopes to study them, as they are so small. To put in simple words, SMACs are tiny structures that tidy up gene expression and maintain genomic stability. These are what we’re working on now.

Why do you think studying this process [X inactivation] is important?

In the long run, studying X inactivation will help us understand general principles of epigenetic regulation in the very first stages of human embryonic development. It’s one of the most beautiful mechanisms that one can study, I feel!

But there is also the promise for regenerative medicine [repairing or replacing damaged tissues or organs] in females. Lots of stem cell therapies don’t fully apply to females, because the stem cells we use to model them lose the inactivated X chromosome in culture and this doesn’t match what happens in the body. Trying to understand these mechanisms will be so important for human health.

You mentioned you do a lot of super-resolution imaging. What made you want to work with microscopes initially?

I know exactly when it was!

During my PhD, I was doing a lot of biochemical work on proteins that regulate chromosomes in dividing cells. During this time I discovered a new histone modification. I made antibodies against it, imaged it, and found that it concentrates at the centromeres [a central region that holds both halves of a chromosome together].

This histone modification seemed to have a structural role, but our microscopes didn’t have the resolution to go deeper. Super-resolution microscopy was emerging at the time, and I decided immediately that this is what I wanted to do – look deep into chromosome structure.

So, I wrote to Thomas Cremer at LMU, a university in Munich. He had the first commercial 3D-SIM [type of super-resolution microscope] in the world. I packed all my things in my car, took the boat over to Italy, and drove over to Munich. It was a high-risk move (as you can imagine!) but I was really interested. This research entirely changed my life.

In 2023, you set up your own lab at the University of Leicester. What has this journey been like? Were there any challenges or exciting moments?

Yes, I came to Leicester because I wanted to try to marry molecular imaging with structural biology, and [my department] is one of the best places in the UK to do so.

I think the best moments were when my first PhD students started; I was so excited! I felt responsibility, but also excitement. The hardest thing was to acquire funding. It was very challenging at first, and I had to be very, very persistent. I worked very hard, and failed many times.

Finally, I was fortunate to secure funding, including the Academy of Medical Sciences Springboard Award, and, a year ago, a Wellcome Trust Career Development Award, and this was a big cause for celebration – now we could do all these experiments I had imagined; going even deeper in resolution and exploring genome organisation and function.

Do you have any advice for people starting out in science?

Scientific research is a lot of hard work – you must be persistent and keep your motivation up, and find a topic that you will be happy working on every day.

And if you don’t get the position you want? You can always find a job or do something in between for a year. You may stress and think that one year is a lot, but at the early stages it matters much less than you think. Challenges are going to be there. Don’t let them break you, and use them instead to empower yourself.

Is there anything you do to relax after a long day?

I like doing yoga. I have two cats, and I love spending time with them! I also like cooking – I’m Greek and I’m a very traditional Greek cook.

Oh, and I’d also like to read more, but at the moment I have more papers to read than books…! In fact, there is a book I recommend to all my students. It’s called The Exceptions: Nancy Hopkins, MIT, and the Fight for Women in Science by Kate Zernike.

Sounds interesting – what’s it about?

Its main theme is the struggles of women in science and how we can try to understand and overcome these biases. They were called “exceptions” because these women had spent years dismissing their individual mistreatment as isolated anomalies, rather than recognising a widespread, systemic rule of discrimination.

This is something I’m really passionate about – today, you see many female PhD students, but much fewer women in higher positions in academia, and I think this imbalance has to be seriously and effectively addressed.

I also loved the book because in parallel it talks about the world of DNA research after the double helix structure was solved, the chase for understanding the proteins that regulate genes, and all these incredible scientists – many women! – that set the foundations for today’s knowledge. Just read it!

Thanks for the recommendation — I’ll definitely check it out. It might become a new blog post soon!

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