Young PIs in action: an interview Giovanni Stracquadanio

Our next interviewee for our ‘Young PI’ series is Dr Giovanni Stracquadanio, Senior Lecturer at the University of Edinburgh and co-director of the Edinburgh biofoundry.

Kostas Vavitsas: Let’s start by telling us about your journey so far.

Giovanni Stracquadanio: How much time do we have? 

I had quite an unconventional path. During high school I studied mostly Greek and Latin, with limited science courses.  But I also had an old computer with me at home. It was the time when the Internet was becoming widely available, and I got drawn into what I can do with it. So I landed a computer-related job at the age of 17.

I did my Bachelor’s, Master’s, and PhD at the University of Catania, at the Department of Computer Science. Programming was natural to me, but to be honest I started getting bored with it. I got a grasp of bioinformatics, and during my PhD I got interested in synthetic biology, due to the connection with mathematics, electronics, and engineering. 

I wanted to switch my research direction to synthetic biology. I moved to the US in 2010 to a postdoc with Joel Bader and Jef Boeke at the Johns Hopkins  University; I was working on the synthetic yeast project, engineering a new genome. This was a project with many challenges, but overall it was a life-changing experience. It really changed the way I do science.

I returned back to Europe in 2014 and did a second postdoc in cancer genetics at the University of Oxford. In 2016, I started my lab at the University of Essex, and I recently moved to the University of Edinburgh, which is probably the best place in Europe to do interdisciplinary research.

Kostas: How was your experience participating in Yeast 2.0?

Giovanni: At that point we had a very good understanding of the genome of yeast and how it is organised, but nobody had done anything close to what we wanted to do. We had to start engineering a genome from scratch, which was very challenging. We had to be conservative in how we designed the chromosomes, as the project was already high risk.

I think that at the end we did a very good chromosome design. What worked very well was that we decoupled design from gene synthesis: the end goal was fixed, but the way to reach there was open to the different partners on how to synthesize and assemble the DNA. We built the first chromosome by assembling 60 bp oligos, while the other  partners involved later in the project used the techniques they thought best…

Coordinating all the different partners was also challenging. My role was to support people and explain design decisions. Keeping everybody to use the same standards and tracking their progress was also difficult. I think the key to success is the fact that we did the design before outsourcing. It was a big project with many moving parts...

Kostas: And now you aim to build mammalian synthetic genome?

Giovanni: The end goal is to build synthetic genomes of higher eukaryotes. I think this will really accelerate research in many fields such as cancer research. How can we  really understand cancer predisposition when the model cells you are using are already mutated and carcinogenic? If you make a designable chassis life becomes easier.

Therapeutics would also benefit. For instance engineering CAR-T cells to aim for certain tumors. Or bioproduction using eukaryotic cells, where we need to make production more efficient.

I draw some comparison with the field of electronics, where we can design and do so many things… I believe that there we are mostly limited by our imagination. We are clearly not there yet in synthetic biology.

Kostas: Can we really combine biology and computer science? What is the challenge of doing interdisciplinary research?

Giovanni: There are two problems. First, if you don’t have a good understanding of biology and the experimental procedures, you cannot do ground-breaking computational biology work. The other is that the concept of an interdisciplinary PI is not often understood by departments, as they need to enlist a PI into a certain faculty. That makes the career path after postdoc really challenging. Edinburgh is quite unique in that aspect, since  centres like SynthSys feature people from various backgrounds and disciplines. I think one should not strive to be the best at everything, but have very good at putting together all the pieces.

Kostas: Moving to more career-related questions, when is the right time to apply for a PI position?

Giovanni: That’s a great question. In my case, I did a first postdoc in the US and a second one in the UK. I had a clear idea of what I wanted to do as PI, a plan for the next few years. Mind you are not a finished product, but a plan. If you are in a good lab, you tend to be independent as a postdoc, and this helps.

Also, look at what’s available at the institutions you are aiming at. And if there is an opening, apply even if you may not feel ready. I have found that people are generally open in giving feedback. If you have a mentor, discuss your next career move. They will give an outsider’s perspective and will point out your strengths and weaknesses. 

Kostas: Do you really need a Science paper to land a PI job in a prestigious institution?

Giovanni: I don’t have a perfect answer on that. It definitely helps, but it doesn’t automatically lead to a position. It also depends on the field. For example mathematicians in general don’t publish in CNS! 

Look, good science pays off. I would advise not to stress on getting a CNS paper, as such a thing depends on circumstances, just focus on doing solid work.

Kostas: What skills would you recommend developing?

Giovanni: Besides science, you need to transition and get an eagle view of what happens in the field. You should have a good understanding of the bigger picture.

But the most invaluable  skill is… try to build a network. Scientists are people first, and if you get along with your peers, they will enjoy working with you and you will benefit from the collaboration.

Kostas: What is different and challenging when you transition to a PI role?

Giovanni: The hardest part is to move away from the lab. When you are a postdoc, you may dream of the day that you don’t have to be in the lab anymore. But it’s way more difficult than you think. It’s crucial to take a step back and become a mentor rather than a micromanager.

Time management is really a key thing.As PI you are supposed to be always on. You are expected to do great science, great teaching, and great admin work. It’s easy to overcommit, and new PIs are prone to that, and it wears you out.

Kostas: What about mobility?

Giovanni: I moved a lot, but I have seen people stay in the same environment from bachelor’s to full professorship, so it’s not a requirement.

Science is made by people, so if you open up and meet new people, see different ways of doing things… it’s invaluable. You develop soft skills and better network. And if you like travelling, it’s a plus.

Kostas: And last question, what is the most important piece of advice you would give to an early career researcher in synthetic biology?

Giovanni: Only one thing, don’t give up.

You don’t do a PhD unless you love science, you don’t get rich by getting a faculty position. PhDs and postdocs are competitive things to do, so if you like what you’re doing you’ll do fine. Don’t try to fit into something you don’t like. And getting advice is in general good, but you should put clear objectives.

Short bio

Dr Giovanni Stracquadanio is a Senior Lecturer in Synthetic Biology at the University of Edinburgh. His lab focuses on data-driven biology lab, in particular on Computer Aided Engineering (CAE) methods for synthetic genomics and machine learning methods for cancer genomics and genetics. Dr Stracquadanio obtained a PhD in Computer Science from the University of Catania (Italy) in 2010. He received postdoctoral training in synthetic biology in Joel Bader and Jef Boeke labs at the Johns Hopkins University working on the synthetic yeast genome. Dr Stracquadanio was a main contributor to the Synthetic Yeast (Sc2.0) genome project, pioneering algorithms and developing software at the foundation of the first synthetic eukaryotic genome. He has also developed tools used in large-scale synthesis projects, streamlining chromosomes engineering and the assembly of biological pathways. In 2014, he moved to the Ludwig Institute for Cancer Research at the University of Oxford to work on cancer genetics, in Gareth Bond’s lab; here, he focused on studying how high-frequency inherited p53 mutations affect the risk of cancer. In 2016, Dr Stracquadanio established the first computational biology lab at the School of Computer Science and Electronic Engineering of the University of Essex, and in 2017 received the Wellcome Trust Seed Award in Science.  In 2019, he joined the School of Biological Sciences at the University of Edinburgh as a Senior Lecturer in synthetic biology and is currently serving as co-director of the Edinburgh Genome Foundry.