Interview

Young PIs in action: interview with Ciarán Kelly


In our next interview of our “Young PI” series, I had the pleasure to talk to Ciarán Kelly from Northumbria. As you will reed below, Ciarán gives a detailed account of his endeavor, and he is now ready to tackle sustainability issues with his research.


Kostas Vavitsas: Probably the most important question of the day: how do I pronounce your name?

Ciarán Kelly: It’s pronounced keer-awn, an Irish Gaelic name. It translates to little dark one, which I interpreted as meaning mischievous one, which I think kinda describes me.

Kostas: You just started your new position in Northumbria University. What is this position and how did you end up there?

Ciarán: Yes, it is at Northumbria University in Newcastle, UK, and I am a Vice-Chancellor’s Fellow. This is a three-year internally-funded university fellowship to start my own research group.

I am from Ireland, and I moved to the UK in 2002 to study genetics at the University of Glasgow. It was there that I was introduced to genetic circuits, while working on the circadian clockss of plants. At the same time, in 2007,Glasgow Uni participated in iGEM, and it was the first time I had heard the term synthetic biology. This really piqued my interest and I wanted to know more about this thing.

After finishing my honours degree and doing some travelling, I decided I wanted to do a PhD. I came back from sunny Australia to live in  Dundee, in the north east of Scotland, where I worked on putting synthetic biohydrogen-producing pathways into microorganisms. The enzymes that produce hydrogen, hydrogenases, are generally ruined by oxygen and require complicated metal cofactors, so there was a lot to try to get right! After a few years of work I managed to produce tiny amounts of hydrogen from my synthetic pathway, a common problem for many metabolic engineers! This made me want to get a better understanding of the field, and in particular an interest in synthetic biology tools.

I then moved to Oxford for a one-year postdoc, which was not meant to last for only a year…

Kostas: What happened?

Ciarán: Well, the PI had recently moved to Oxford from Imperial, and after 6 months he announced he was leaving to go to the US.

After the initial shock the situation worked well for me. I was able to start some independent projects, I negotiated a research budget with the department and started some really fruitful collaborations, including one with Prof. Antonis Papachristodoulou in Engineering Science

As I was living in London and commuting daily, at the end of this year I moved to London and the Centre for Synthetic Biology and Innovation at Imperial College. I joined the group of Dr. John Heap, a new PI who was interested in metabolic engineering of non-traditional microbes. He also wanted to focus on achieving high product yields. I worked on various projects in different organisms, including cyanobacteria (your organism of choice, right?). I dipped into the cyanobacterial world, and I found there was a lack of good tools. So I decided to work in that space and came up with a few useful tools to control gene expression in cyanobacteria, such as inducible promoters,  terminators etc.. 

At this stage, I was encouraged to start applying for independent funding. I didn’t have a “superstar” paper, but I’m starting to get some solid first-author publications out. I took a short-term contract in Oxford to finish up some experiments for a paper with the engineering group. This involved engineering small RNAs for use in synthetic negative feedback circuits and working closely with modellers, which was a fun experience. I think when I started my PhD I was initially sceptical on how “engineerable” biology could be, but now I’m now a full convert! I then applied for a LOT of fellowships, which although they were rejected, got good reviews, encouraging me to keep going.

And then eventually this opportunity came up and now here I am!


Kostas: There you are. What is the theme of your current research?

Ciarán: That’s a good question, I ask it to myself all the time. My interests are quite varied, but in general my interests are in metabolic engineering of complicated pathways for sustainable biomanufacturing. I am interested in optimising metabolic routes that are, say, 15 catalytic steps long. Producing and maintaining all of those enzymes at the right levels in a non-native host is a big challenge, and I want to use new and existing synthetic biology tools to make it reliable.


Kostas: When is the right time to apply for a PI position?

Ciarán: I can’t say that there is an answer that fits everyone. In my case, I was a bit slow initially in getting publications. So even though I felt ready intellectually and experience-wise some time ago, I had to be realistic and take into account that you need good papers and an interesting research story. So it’s a trade-off between getting those papers and spending a substantial amount of time on putting together a  strong application.

I learned a lot from applying for a postdoctoral fellowship. It makes you start to come up with a good proposal. We hear all the ways synthetic biology can and will change the world, but you need to think about what part you can play in this mission. The more proposals you write, the better they become, as you get feedback which you incorporate in later applications to tweak the ideas etc.


Kostas: But there are also differences between PI and fellowship applications, right?

Ciarán: There are similarities, but also notable differences. As PI positions usually have the title of lecturer, they give emphasis on teaching qualifications – something that some of us who have been in research-only roles tend to ignore. I would try to take up teaching duties whenever you can, for example, asking about doing some tutorials, lectures etc.


Kostas: Do you feel that your training as a PhD and postdoc prepare you adequately for independent positions?

Ciarán: I was very lucky with the mentors I had. They were great at sharing insights into how science is done and how a lab runs! I recommend to seek mentorship as much as possible. Your supervisor, other experienced postdocs, fellows and other friendly PIs.…scientists are never shy to give advice if you ask! Of course you will need to filter it and keep the bits that work for you. This will help get you there and prepare you for independence.

But there is another thing to keep in mind. I don’t expect to be suddenly transformed into the world’s best PI. And I think that’s okay! It’s just another stage in my career development, which will happen in any new role. I’m seeking feedback from  colleagues and listening, I’ll try out a few things, I’ll make mistakes, and hopefully along the way I’ll become a better PI.

 

Kostas: A comment on mobility? You moved to quite a lot of places.

Ciarán: Not as far as you!

Kostas: That’s true, but I’m asking you…

Ciarán: Lots of it was due to circumstances, but I was always looking for good opportunities to go to new places, and I have benefitted from that. I have seen a few different work cultures. That said, I’m happy that I could stay for three good solid years at Imperial and get some things done.

Sometimes you have to move, like to do a particular piece of work or collaborate with a certain group, or live with your partner! It’s common and easier to do early in your career, as at some point  you might want to set down some roots .


Kostas: Last question. How do you feel about your new role?

Ciarán: I’m really excited! I was offered this position in April and I feel great about it. Now it’s time to get some grants, recruit students and test out my own research ideas. I really want to be a good mentor for trainees, to offer them the support my mentors gave me.

I’m very passionate about tackling big challenges surrounding sustainability. It’s very inspiring to see so many like-minded young researchers, for example in your “Young PIs” series, who want to work on climate change and sustainability with their research. Let’s do it!


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Ciarán was born in Dublin, Ireland. He graduated from the University of Glasgow in Scotland in 2007 with a BSc. (Hons) in Genetics. After a year of working at the Beatson Institute for Cancer Research in Glasgow, he went travelling for a year and a half before returning to start a PhD in the lab of Prof. Frank Sargent at the University of Dundee, Scotland. Following his PhD, he had postdoctoral positions at Oxford University, Imperial College London and Newcastle University. He recently started at Northumbria University in Newcastle as a Vice-Chancellor’s Fellow in Cellular and Molecular Biosciences. He’s a prolific tweeter and you can follow him and say hi @kellier13 on Twitter.

3 Questions for Dr. Yolanda Schaerli

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In our latest post in our “3 Questions for” series, we have the joy to Interview Dr. Yolanda Schaerli. Yolanda is an assistant professor of synthetic biology at the University of Lausanne, Switzerland. Her research group uses synthetic biology to understand the mechanisms, properties, and evolution gene regulatory networks.

   

When and why did you move into the field of synthetic biology?

During my studies in biology, I became fascinated with engineering biological systems. The goal of my PhD project was to improve enzymes by directed evolution (performed in microfluidic water-in-oil droplets). When looking for a post-doc position, it was clear that I wanted to move into the emerging field of synthetic biology and decided to build synthetic gene regulatory networks. The research currently ongoing in my lab involves engineering synthetic constructs in E. coli that help us to understand underlying biological principles and fundamental properties of biological systems, with a focus on gene regulatory networks involved in pattern formation.

 

In which areas do see the main challenges and opportunities for synthetic biology?

Synthetic biology has the potential to fuel the next industrial revolution. Engineered biological systems have potential applications in almost every aspect of our lives, for example by providing novel approaches to detect and treat diseases and to produce fine chemicals, biofuels and smart materials, just to name a few. Synthetic biology will hopefully contribute to transition to a more sustainable society that avoids climate change and environmental degradation.

The big challenge is to realize this potential. This will require moving from “proof-of-principle” circuits to robust systems that reliable function in real-world settings. It will also require addressing ethical and regulatory issues.

 In basic science, synthetic biology provides us a complementary approach to study the mechanism, organization, function, and evolution of natural biological systems and processes. By building simplified versions of complex natural systems, we can focus on the elements of interest, while avoiding confounding factors. I hope that this approach will become more accepted and valued in the scientific community.

 

What is the most important piece of advice you would give to an early career researcher in synthetic biology?

I don’t think there is a single advice that applies to every early career researcher. I would like to mention three points that I think are important:

It is not enough to do great science; you also need to be able to communicate it. Good writing and presenting skills truly make a difference. If necessary, take some courses and practice as much as you can.

I often observe that PhD students and post-docs start too late thinking about what they would like to do next. If you only apply for post-doc positions after submitting your PhD thesis, you are likely to have an (unfinanced) gap, which might for example be problematic for your visa situation. Consider that it easily takes 10 months or more from applying to a fellowship or grant to starting the new position.

I would also like to point out that leaving academia is absolutely no failure and should be an option from the beginning. There are so many interesting jobs outside academia, why not considering them?

Young PIs in action: Interview with Stephen Wallace

In our next installment of our Young PI series, Jo Sadler interviews Stephen Wallace, group leader and lecturer at the University of Edinburgh.

 

Jo Sadler: How did you find your transition to PI? Any unexpected challenges?

Stephen Wallace: Goodness…how long do we have?! The entire process was scary, but an amazing amount of fun at the same time. I think most of the challenges I faced were somewhat unexpected – you are, after all, suddenly required to adapt to a job that requires a completely new set of skills. However, research is all about venturing into the unknown so perhaps the transition to PI is simply another manifestation of this. I found the isolationism of the job quite challenging at first – going from working with a group of people in a lab to working on my own in an office was a big change.

Luckily for me, the Institute for Academic Development at the University of Edinburgh runs a brilliant Research Leadership Program, which all new PIs are enrolled on. Also, I was fortunate to be selected for the 2017 Scottish Crucible, which was an invaluable opportunity for me to engage with the media, local government and to connect with other early-career researchers in Scotland. Both of these programs helped me tremendously during my first year as a PI.

  

Jo: Is E. coli the ideal environment to perform chemical reactions? What are the pros and cons of performing chemical synthesis within/associated with a cell?

Stephen: What an exciting question! To be honest, this is what we are exploring right now. One of the main challenges is their perceived incompatibility. Historically, the fields of chemical and biological synthesis have been considered as mutually incompatible – i.e. metal-based chemical catalysts are inactive under the conditions required to support a living organism and are toxic to cells. However, our research is showing that this is isn’t always true. For example, we’ve recently discovered a chemical reaction that is accelerated inside the membrane of living E. coli cells (it is, after all, similar to an organic solvent!). The potential for innovative research in this field is tremendously exciting and will continue to rely on the combined efforts of both synthetic biologists and synthetic chemists.

For now, all I can say for sure is that unexpected things keep happening when we try-out synthetic reactions in the presence of living cells, and these effects can often have a positive influence on the reaction outcome.

 

Jo:You have worked both in the UK and the US. Any striking cultural differences between the research environments? 

Stephen: Day-to-day life as a researcher in the UK/US is very similar. I’m always impressed by the “go get it!” attitude of American science, whereas I think British researchers tend to be more constrained and methodical (which isn’t necessarily a bad thing). This really inspired me during my time in Boston and LA and has certainly influenced my ethos as a PI in Edinburgh. In the absence of empirical data, the phrase “this won’t work” is banned in our lab.

  

Jo: Is mobility important for a researcher?

Stephen: I get asked this question a lot. Many scientists seem to believe that international experience is a prerequisite to a successful career in research. I strongly disagree with this mentality, but I do encourage my students explore options abroad when thinking about their next career move. I think it ultimately comes down to science and strategy (in that order) – where are the experts in your field? Where are the emerging techniques being developed, and can you bring something new/complementary to this field? I can always spot the scientists who move abroad simply to work for “the big name” and there’s often a downstream mono-dimensionality to their research as a result.

 

Jo: What is the one most important piece of advice you would give to a synthetic biology early career researcher?

Stephen: Never let an unexpected result go unexplained!

 

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Stephen Wallace is originally from the small village of Thornhill in Dumfries and Galloway. He graduated from the University of Edinburgh in 2008 with an MChem in Medicinal and Biological Chemistry. He then moved to the University of Oxford to pursue a DPhil in Organic Chemistry in the laboratory of Prof. Martin Smith. In 2012 he took up a MRC Postdoctoral Career Development Fellowship in the laboratory of Prof. Jason Chin at the MRC Laboratory of Molecular Biology in Cambridge. In 2014 Stephen moved to the U.S. as a Marie-Curie International Research Fellow, where he worked in the laboratory of Prof. Emily Balskus in the Department of Chemistry and Chemical Biology at Harvard University. During this time, he was also a Visiting Associate Department of Chemical Engineering at MIT, hosted by Prof. Kristala Prather. In 2016, Stephen carried out the Return Phase of his Marie Curie Fellowship in the laboratory of Prof. Steve Ley in the Department of Chemistry at the University of Cambridge, where he continued his work on combining synthetic and biological strategies for chemical synthesis. In 2017, Stephen returned to the University of Edinburgh as a Group Leader and Lecturer in Biotechnology in the School of Biological Sciences, where his lab explores scientific opportunities at the interface of organic chemistry and synthetic biology. Stephen is currently a Visiting Associate in the Department of Chemical Engineering at the California Institute of Technology, hosted by Prof. Frances Arnold.

Young PIs in action: Interview with Iro Tsipa

In our next post of our young PI series, I had the pleasure to interview Iro Tsipa, who will shortly start in her new role as as a Lecturer in Environmental Biotechnology at the University of Cyprus.

Kostas Vavitsas: You recently moved to Cyprus from the UK and you are going to start your own lab very soon. What are the most striking differences between the two research environments?

Iro Tsipa: In the UK, I was working in a world-leading institution, Imperial College London, and in a cutting-edge research centre, SynbiCITE. So, the research could run smoothly in terms of support in equipment and consumables, communicating ideas, being able to attend and participate in conferences.  In Cyprus, these are not for granted, I had to prioritize the tasks in the projects I participate in, as the budgets are much lower. I feel more responsible for the choices I make. This was quite challenging in the beginning but now I understand better the priorities of a lab and a project and it helped a lot to be prepared for my next job.

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Kostas: Do you feel prepared to start your new role?

Iro: I’m very excited to start working as a PI, have my lab and contribute to realistic solutions for environmental bioremediation and bioprocessing. I feel prepared about that. It seems like a natural next step to my academic career. The main challenges are: (i) get funded to be able to have the necessary equipment and working environment, (ii) find young people who share the same passion for environmental biotechnology to make a strong team and (iii) make a multi-disciplinary network of partners and collaborators who appreciate science to share ideas and try to answer key scientific questions.

 

Kostas: What is the true potential of environmental biotechnology and synthetic biology? Any interesting application that came up recently or will be out soon?

Iro: Environmental sustainability is at the core of the challenges of synthetic biology community. Engineered microbes and synthetic microbial consortia can substantially assist in limiting CO2 levels, recovering phosphorus, bioremediating and biodegrading resistant and toxic compounds that natural strains cannot process (yet)… Plastics and micropollutants biodegradation assisted by engineered microbes is an interesting field of emerging concern, which has attracted attention in recent years. Further, bioprocessing is a bottleneck in synthetic biology. We recently submitted a paper with my academic mentor, Sakis Mantalaris, and close collaborator, Gizem Buldum, of a kinetic model of synthetic genetic circuits predicting product formation towards microbial cell factories bioprocessing. I hope that this project will provide a different point of view of mathematical modelling and process intensification in synthetic biology.

Kostas: What is the single most important piece of advice you would give to an early career researcher in synthetic biology?

Iro: I would say ‘follow your own path’, find what fascinates you the most based on your background and knowledge, do your own research in the literature and start building on. Also, perform a thorough research of which groups work on similar projects and try to be inspired. Research and science are based on team efforts which can result in a great individual result.



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In August 2019, Argyro (Iro) Tsipa will start working as a Lecturer in Environmental Biotechnology in the Department of Civil and Environmental Engineering and Nireas International Research Centre, at University of Cyprus.Currently, she has been a Senior Researcherin the Department of Environmental Science and Technologyat Cyprus University of Technology. She obtained a Diploma in Chemical Engineering from the National Technical University of Athens, an MSc in Chemical Engineering with Biotechnology from Imperial College London where she also got her PhD in Bioprocess Systems Engineering. Before her current appointment, she worked as a Research Associate at the UK’s National Innovation and Knowledge Centre for Synthetic Biology (SynbiCITE) and the London DNA Foundry. Iro is considered as an expert in transcriptomics and proteomics. She has been instrumental in developing an integrated experimental-modelling framework to design optimal bioprocesses with applications in Industrial and Environmental Biotechnology, and Synthetic Biology. She developed and is responsible for the molecular biology facility of her current lab and the OzoneBioPro project developing a hybrid ozonation-bioremediation treatment of drill cuttings of the drilling operations in Cyprus.

 

Young PIs in action: Interview with Kaspar Valgepea

Our next blog in our Young PI series features Kaspar Valgepea (lab website), a group leader from Tartu University (and old lab mate of mine at the University of Queensland).


Kostas Vavitsas: You have worked both in academia and in the industry. What do you miss and what you don't miss from working in a company such as Genomatica?

Kaspar Valgepea: My work experience in Genomatica was a bit special, as I was there as a Visiting Scholar and I ran an independent project. Thus I did not exactly have “corporate” deadlines, which maybe let me work under less stress. Nevertheless, the momentum of work and research in such a fast-growing biotech company was impressive and addictive in a good way. I greatly enjoyed working together with highly ambitious and professional people who had the highest goal: to make biology work for mankind. My co-workers, but most importantly the work atmosphere at Genomatica, truly inspired me to dream big and set the highest goals.

One thing that I do not find in academia is this special teamwork atmosphere where a significant number of people are all working towards one single goal. There is nothing I can think of that Ireally don’t like in the industry, but I would say that one benefit of academia is the freedom to be curious and investigate things that might not necessarily lead to near-term financial gains.

Kostas: Biotechnology and synthetic biology have set high expectations on potential applications and societal impact. Where do you see the field in the next 5-10 years?

Kaspar: Indeed, biotech and synbio have set the bar high but I am optimistic that they will deliver! I think we need a few more breakthroughs that are obvious for both investors, science funders, and people in general to kick-start the snowballing effect. The revolution has clearly started, just last week I felt great when I found out that there is a company in Estonia that is making biodegradable plastic bags from the 1,4-butanediol produced by the Genomatica process! And there will be an increasing push towards sustainable solutions, in terms of biotech, for chemicals and fuels due to climate change. Europe has set several ambitious goals recently, e.g. the new Renewable Energy Directive, single-use plastic ban, waste recycling etc. These actions are essential to fast-track innovation both in academia and industry.

One focus of Kaspar’s research is systems biology of gas fermentation, recently exemplified in a Cell Systems paper (DOI:  10.1016/j.cels.2017.04.008 )

One focus of Kaspar’s research is systems biology of gas fermentation, recently exemplified in a Cell Systems paper (DOI: 10.1016/j.cels.2017.04.008)

I am personally most excited about the idea of seeing waste as a resource for its conversion into sustainable fuels and chemicals through bioprocesses. I am obviously biased, but I see that gas fermentation technologies for capturing waste and renewable carbon have a huge potential. LanzaTech is proving this by currently operating one and building four industrial scale plants world-wide. There are many other examples and exciting fields, I highly recommend the recent Economist story on synbio for a good overview.

Kostas: What was the biggest challenge you had to face in your professional life so far?

I think things have worked out quite smoothly for me so far. I was lucky to be invited to join the unique lab of Professor Raivo Vilu during my Bachelors in Estonia, and enjoyed working there a lot until my PhD with a few stints abroad in between to the US and Japan. For a postdoc, I searched around quite intensively and it paid off. My postdoctoral experience at Esteban Marcellin’s lab at The University of Queensland was probably as good as it gets, for me at least. I think these steps paved a good way to the startup of my own lab back home in Estonia with help from Professor Mart Loog. And this startup I have been doing since March is surely the biggest challenge I have faced. I have to set up an experimental lab basically from scratch, hire people, start innovative projects, collaborate with industry... a lot on the plate. We will see in about four years how did I do. I am super excited to have this privileged and great opportunity. Fingers crossed that I can transform this excitement into creating a lab where people want to work and can do cutting-edge science!

Kostas: How easy was it to transition from postdoc to PI? Was as you had imagined it?

Kaspar: As I said above, the transition went quite smoothly. I thought it would be harder but it might have turned out smoother due to a few things. First, I started thinking and planning about post-postdoc during the first half of my postdoc. This might help you to have a clearer vision about potential trajectories early on, so you could react faster once options pop up. Second, I was networking and keeping old contacts active in light of potential future research options or collaborations. These two things likely had an important effect on me being awarded two personal research grants and on being selected as the group leader of the ERA Chair in Gas Fermentation Technologies.

Kostas: If you could change one thing in your career trajectory, what would it be? What is the single most important piece of advice you would give to an Early Career Researcher in synthetic biology?

Kaspar: I was happy to conclude that I would actually not change anything! If research at the first lab I worked in in Estonia had not been that exciting, I would have potentially went to do MSc or PhD abroad. I did not do that as I believed that exciting research will lead into results and these are more important later than “just” having more locations on your CV.

My advice for an ECR would be to dream big and then work towards that dream as hard as possible while maintaining work-life balance. If you are passionate about it and enjoy it all along, I think you are all good.

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Kaspar Valgepea is leading the ERA Chair in Gas Fermentation Technologies at the University of Tartu that employs gas fermentation technologies together with systems and synthetic biology methods to address global challenges of biosustainability