Mycocyclosin-based photoaffinity probes

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The key research goals in this project are:

• To elucidate the molecular target of mycocyclosin and unravel its role in Mtb biology.
• To develop new targets for the development of anti-TB drugs.

The details

Professor Munro and Professor Hutton have an established collaboration investigating enzymes from the human pathogen Mycobacterium tuberculosis (Mtb), with the overarching aim to characterise their functions and exploit these proteins as novel drug targets.

The gene encoding for the Mtb enzyme CYP121 is essential for mycobacterial viability. CYP121 generates the natural product, mycocyclosin, an oxidatively modified cyclic dipeptide. It is therefore postulated that mycocyclosin has a crucial role in Mtb viability – yet the biological role of this compound remains unknown.

Determination of the function of mycocyclosin in Mtb proliferation will present new opportunities for the development of novel anti-TB drugs.

Graduate researcher profile: Hannah Ryan

What did you do before you started your PhD?

Before I began my PhD I completed my MSc (Hons) in Chemistry at the University of Melbourne. I worked with Professor Craig Hutton researching the ring expansion of cyclic peptide hydroxamates.

What are the challenges of your research role?

COVID-19 has a huge impact on the way we work as researchers and has tested and continues to test my resilience. It can be very challenging to maintain motivation and consistent work when there are many disruptions beyond my control. However, I have been very grateful for the chance to grow to be a more independent researcher as I have moved from Masters to PhD and to adapt to the challenges of taking on more responsibility in my lab environment.

What is the best part of your research role?

Working on an international collaboration is a privilege and one of my favourite parts of my PhD research. My work has been with peptide chemistry but with our Manchester collaboration I will have the opportunity to work in biochemistry and take the molecules I make and test them on bacteria. The chance to work on a project in which I have the opportunity to learn about new fields of science and follow through on my research into experiments that I wouldn’t normally be able perform myself is very exciting.

Where do you wish to go after your PhD? Do you want to enter industry or continue doing more research?

I am currently interested in keeping both options available to me, however I am leaning more toward a career in industry. I love communicating and sharing my research so I think I would find a lot of fulfilment in an industrial environment.

Supervision team

• The University of Melbourne: Professor Craig Hutton
• The University of Manchester: Professor David Leys, Professor Andrew Munro