3 Questions

3 Questions for Dr. Louise Horsfall

Those who attended our April symposium remember an engaging diversity breakout session led by Dr. Louise Horsfall. Now she provides with her own insights at our new "3 Questions For" interview.  Louise, a Lecturer in Biotechnology at the University of Edinburgh, is interested in multidisciplinary challenges involving Biotechnology and Synthetic Biology. Read more about her research here and follow her on Twitter.

 

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

During my first postdoc I received some great career advice and was pointed in the direction of synthetic biology as a new and potentially important field. Once I found out a little more about the area, I made sure that my next postdoc position was in a synthetic biology lab.

 

What is the single most important piece of advice that you would give to a current PhD student or a post-doc?

Irrespective of field, I think that PhD students and post-docs need to consider the environment they want to work in, as well as the research area, when choosing laboratories. I was completely inspired when I got to work in a supportive, interdisciplinary research environment that encouraged independence, industrial collaboration and outreach, and it was only then that I realised with certainty that I wanted a career in academia.  

 

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

I think synthetic biology offers us the opportunity to move towards a more sustainable and circular economy, but it is a challenge to understand and appreciate just how far-reaching this opportunity actually is. With a technology that includes biology in its name, it is understandable that it is assumed that any impact will be on the bioeconomy but we need to challenge ourselves to think beyond this.

 

3 Questions for Prof Birger Lindberg Møller

The series continues with "3 Questions For" our academic sponsor Professor Birger Lindberg Møller. Professor Møller is Director of the Center for Synthetic Biology at the University of Copenhagen and Distinguished Professor at the Carlsberg Laboratory. Read more about his research in the area of Plant Biochemistry here and check out his TED talk on Plant power featured on our website.

 

How did you move into the field of synthetic biology?

Working with plant specialized metabolism for my entire career in science, the modular nature of the metabolic pathways became apparent. Bio-Engineering based on an understanding of how these modules interact became a key feature of our research and was fully aligned with and contributing to defining the concepts of synthetic biology and the underpinning share-your-parts principle and involvement of the do-it-yourself communities. Based on our research contributions, we were awarded a 16 million Euro grant from the Danish Government in 2009 to establish a Center for Synthetic Biology bridging plant biochemistry, bio-physics, nano-science, neuroscience, ethics, law and communication. This interdisciplinary approach to synthetic biology has enabled us to engage in and interlink basic as well as applied research within the natural sciences in parallel to maintaining vivid upfront positive and mutually highly awarding discussions within ethics, communication and law. These discussions have often guided the research of our synthetic biology center within natural sciences into entirely new directions. On example is our efforts always to obey the concept of working with nature instead of against nature in our engineering efforts e.g. within light-driven synthesis of structurally complex diterpenoids.    

What is the single most important piece of advice that you would give to a current PhD student?

Follow your idea and pursue what excites you. When you are personally engaged, you accomplish a lot more. Choose to work in a research environment where people respect each other and want to and are able to collaborate. Choose a PhD advisor who understands how to manage to work under the radar of university administrators and a head of department who lack scientific competences and empathy, cannot manage to communicate difficult issues and who have to refer to figures in excel sheets based on simple metrics when they prioritize.  

What are the major limiting factors to progress in the field of synthetic biology right now?

A basic understanding of the functions of modules in living cells. Lack of high impact journals who have established an editorial board and set of referees able to provide justified evaluations of highly interdisciplinary research contributions resulting from advances within synthetic biology. As a plant biochemist, I thought it was a timely and well thought out decision to establish the journal Nature Plants considering the importance of plants and plant research to offer science based solutions to the global challenges humanity is facing within climate change, food security and sustainably energy production. However, this mindset does not seem to have been the motive. Focus on crop plant research and on research topics e.g. elucidating the effects of climate change on food security and quality and pest resistance in natural environments is not apparent. But as a PhD or post doctoral fellow in a rich industrialized country, please realize that you should never let you influence or be directed by barriers set up by persons and systems who do not manage to adapt to current demands. There are no acceptable excuses if the limiting factors for your personal performance is not your personal intellectual capacity, ability to work hard, collaborate and be a trustworthy and generous person. Please keep in mind that synthetic biology sets no limits for your personal performance and ideas to be pursued. So go for it and good luck.

3 Questions for Prof Roman Jerala

For the second part of our series, we had "3 Questions For" our academic sponsor Professor Roman Jerala who is head of the Laboratory of Biotechnology at the National Institute of Chemistry in Ljubljana and multiple winner of the Grand prize at iGEM competitions leading Slovenian teams. More information about Prof Jerala's research can be found on his lab website.

 

 

When and why did you enter synthetic biology ?

I only became aware of synthetic biology through the iGEM student competition, which is when we made our first steps in this direction in 2006.  iGEM projects also led to our diversification into different field of synthetic biology while all the time maintaining an eye on health applications. Currently, we are trying to combine our interests in immunology with synthetic biology, which I think can be quite a powerful combination. The main attraction of synthetic biology for me is the opportunity to apply larger degree of creativity than just by exploring natural phenomena. Synthetic biology is also a very powerful investigational tool to explore different “what if” scenarios or to understand natural processes in the Feynmanian sense.

What do you see as the most important directions of synthetic biology ?

I am confident that the next technological revolution will have strong biological character as soon as the ability of rational bioengineering advances to the level we use in engineering and electronic circuit design. In the last half century, molecular biotechnology managed to harvest some of the potentials of cell factories, particularly for the production of increased amounts of natural or modified natural compounds. A major effort in synthetic biology is currently applied to microbial cell metabolism which supports the boom of metabolic engineering that is already being applied in the industry. Future efforts should in my opinion be directed towards exploring the potentials and pushing boundaries of the field rather than giving emphasis on the immediate application or compiling registries of existing natural parts. Those are clearly useful but will provide only incremental steps forward. Strong collaboration and interconnection between most creative scientific groups in the field is essential for the scientific leadership and for the opening of new horizons. I expect that the next generation synthetic biology will move strongly towards introduction of principles that have not evolved in the nature.

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

In my opinion, synthetic biology has great potential in medicine, and some synbio solutions may reach clinical applications within the next decade. I believe that synthetic biology can enhance application of stem cells or offer an alternative to them. Rational design of biological systems may be able to avoid the seemingly unavoidable development of microbial resistance, for example by functional targeting essential microbial functions rather than specific microbial components. Targeting of cancer-associated processes may also be able to prevent the escape from the immune response. The potential of CRISPR/TALE technology is clearly game-changing for the implementation of synthetic biology in health applications. Processing information in biological systems will not be able to compete with electronic systems in terms of speed and reliability–but in terms of manufacturing cost, energy efficiency, sustainability, and complexity, biological systems offer a very attractive alternative. In next generation of synthetic biology, we should aim to design advanced information processing biological devices not simply following the electronic computer logic but building on the specific advantages of biological systems. We should aim to advance the design of information processing from the genetic regulatory circuits towards the protein and membrane potential-based designs, which should improve the time constants by several orders of magnitude or, to say it poetically, to function at the speed of thought. One of the important opportunities for synthetic biology certainly lies in harnessing biopolymers as the building blocks of new complex assembles, which can be produced by cell factories. Rationally designed bionanomaterials can have properties that have not evolved in the nature. Designed polypeptide-based modular nanostructures as demonstrated by our single chain designed polyhedron (Gradišar et al., NatChemBiol 2013) has so many potential directions of advances that it is difficult to select the main priorities.

3 Questions for Dr Tom Ellis

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For the first of our series "3 Questions For" we talked to Dr Tom Ellis, one of our academic sponsors and senior lecturer in synthetic biology at Imperial College London. Read more about Dr Ellis' research on his lab webpage and follow him on Twitter @drtomellis

How did you become a synthetic biologist ?

I chose my PhD in 1999, and although synthetic biology wasn't on the radar in those days, I found myself researching ways to control promoters using drugs. By the time my PhD was finished in 2004, I saw papers emerging from the nascent synthetic biology community that really appealed to me. They were using rational approaches to engineer of promoters to control gene expression in microbes, and because they were doing it with standardised parts even a group of students were able to get results like the famous E.coli 'Hello World' photo that got the front page of Nature in 2005. I quit my day job at a drug development spin-out, visited the organisers of Cambridge's iGEM team and wrote to synthetic biology researchers asking for availability of postdoc positions. Many very busy US and UK professors were kind enough to give me detailed personal advice while I was searching - Pam Silver and Jim Haseloff, especially - and after a few months I was lucky enough to be starting as a postdoc with Jim Collins at Boston University. It's weird to think I just dropped a nice job at a young company in London simply because I was so excited by the research papers I was reading, but that's the way I was and I totally have no regrets (even though I missed out on share options when the spin-out sold for $440 million in 2013!)

Looking back to your time in graduate school, what piece of advice would you give someone who has just commenced their PhD research ?

Take ownership of your PhD project. No-one else is going to do your PhD for you and no-one should care more that its working or not working than you. If you're a PhD student then chances are that you are an intelligent, independently-minded adult and someone at your level in life should be capable of starting-up a small business or having a management role in a company. You have to think of your PhD project as your own business, and not the pet project of your supervisor. Nine months into my own PhD, I realised I wasn't happy going down the route I'd been given when I started, so I went and found my own collaborators and devised a related project that I thought would be much cooler. When I told my supervisor I wanted to change the topic he was delighted, because I'd taken charge and he could see I was now self-motivated to do my project making life much easier for him. Nothing is worse than the student who is 2 years into their PhD and moaning that they got given a bad project and hoping their supervisor will wave a magic wand. 

What do you think is presently the major limiting factor for progress in the field of synthetic biology ?

It used to be DNA assembly, but with methods like Golden Gate that has become something straightforward and even automatable. The next hurdle was a lack of predictable and orthogonal parts, but many awesome papers in the last 5 years have now given us huge libraries for all the key parts, especially in E. coli. So right now the limiting factor for progress has got to be the cell itself. I could get a robot to assemble a cascade of 20 different logic gates in a plasmid within a week but transforming this into a cell and getting it to function would be tough. Why? Because a microbial cell like E.coli is an incredibly complex network of interactions all geared towards fast growth in rich food. Throwing in extra tasks for it to do that interact with all the cell machinery is like handing a Rubik's Cube to a Tour De France cyclist as they scale Alpe d'Huez - it's going to slow them down and probably not end with a happy outcome. A much better understanding of the interactions between a synthetic construct and the cell is what we need now to make the field move forward. Hopefully whole-cell simulations of microbial cells will soon become good enough to do this.