Francesca Ester Morreale is a postdoc in the lab of Tim Clausen. She studied the protein degradation machinery of bacteria and developed BacPROTACs, a technology that could be applied to antibiotic discovery. She published her work in the journal Cell. Ester will start her own group at The Francis Crick Institute and will be hiring lab members soon.
How was your experience looking for a Principal Investigator position?
I started looking for a position when my latest paper was almost published. Early on, I was awarded a grant to start my group at an Italian research institution, which was a great opportunity, and I knew I wouldn’t settle for anything less than this grant could offer. However, I had also applied to different positions around Europe, and I was invited to several informal seminars and interviews, including one at the Francis Crick Institute. I wanted to find the best place and support for my research.
How did you know the Crick was the right place for your plans?
Turning down the offer I had from Italy was not easy, but when I was at the Crick for my interview, I really felt that my research would fit in. I was impressed by the institute, including my future colleagues and the infrastructure. The Crick’s environment and the competitive starting package convinced me that the Crick was the best place for my future research and career.
How did your scientific journey begin?
I started in Messina, one hour away from my hometown in Sicily. I studied Pharmacy and, during my Master’s, I realised that I really enjoyed doing research. My supervisor in Messina asked me if I wanted to stay to keep working with computational methods applied to drug discovery, and I applied to the PhD programme there. The issue was that, although I liked computational methods, I also really wanted to work in the lab, at the bench.
How did you make that happen?
I had the opportunity to spend six months abroad as a research stay. I contacted Alessio Ciulli, a group leader who was at Cambridge University back then. He was using fragment-based drug discovery, biophysical methods, X-ray crystallography, and other techniques that I wanted to learn. I talked to Alessio, and he agreed to interview me – I was very excited about the idea of going to Cambridge and doing lab work. My perseverance paid off. After six months of lab experience, I returned to Italy and defended my PhD. Then came the time of my first postdoc.
I believe that being a good supervisor – and a good manager in general – requires certain soft skills, requires actively training those skills.
Tell us more about your postdoc experiences.
Alessio moved to Dundee in Scotland and introduced me to Helen Walden. They had a collaborative project in mind that would fit my expertise and objectives: it was about targeting a ubiquitin-conjugating enzyme with fragment screening, so it was a good mix of computational methods and wet lab work. I spent three years in Dundee as a postdoc. At that time, I wasn’t ready to start my independent research because I had switched fields, learning a whole new set of skills when I started doing wet lab work, so I joined the lab of Tim Clausen at the IMP for a second postdoc. This time, I started working with targeted protein degradation, a technology that was being developed for human cells in Alessio Ciulli’s lab, among others. I met Tim at a conference where he presented protein degradation pathways in bacteria, and it looked like these pathways were conceptually similar to ubiquitin-proteasome systems, so targeted protein degradation could also be developed there. I thought this was a great research opportunity, and so far, unexplored.
What did you gain from this second postdoc?
I found my project really exciting and learned anything that could help me develop my ideas, including cryo-electron microscopy. We also collaborated with Boehringer Ingelheim as I started as member of their newly established postdoc programme. I enjoyed discovering the interface between fundamental research and industry.
What’s your lab going to investigate?
Together with the Clausen lab, we found a way to selectively degrade proteins in bacteria through a specific proteolytic complex called ClpCP. I want to develop this concept further and explore other targeted protein degradation strategies for different types of bacteria. To do this, we need to understand the molecular mechanisms that regulate cellular proteolytic machines. Ultimately, targeted protein degradation could help us expand the number of available antibiotics and target proteins previously considered ‘undruggable’. My lab will take a multidisciplinary approach to answer these research questions, integrating structural biology, chemical biology, and microbiology.
What kind of people are you looking to hire?
I will first look for a research technician to help me set up the lab and bring in some microbiology expertise. I’ll also have funding for postdocs: I will be looking for a chemist and a structural biologist with experience in cryo-electron microscopy. PhD students will be recruited through the Crick PhD programme – I’ll be flexible as to the candidates’ background, should it be in microbiology, structural biology, biochemistry, or others.
What kind of supervisor do you want to be?
It’s important to me that all lab members feel inspired to do excellent science with the full support of their supervisor. A good relationship between lab members is crucial to keep a positive environment where everyone is happy and motivated to work productively. I will encourage critical thinking and continuous learning, which are essential for personal scientific development, and contribute to the success of individual projects.
Who is a supervisor you look up to?
I was lucky to have good supervisors throughout my career. Helen Walden’s approach to managing her lab was particularly inspiring. I believe that being a good supervisor – and a good manager in general – requires certain soft skills, requires actively training those skills, and Helen did it very well. She was also encouraging creativity and giving students and postdocs the freedom to explore their ideas. I still ask her for advice now, so in a way she’s still my mentor.
Published in February 2023.
---
Interested in Ester’s profile? See her brand-new lab page here: https://www.crick.ac.uk/research/labs/francesca-ester-morreale