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.

iGEM Aachen 2019: Plastractor

by Alina Egger and Yasmin Kuhn

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Currently everybody talks about environmental pollution by plastic. But not only big plastic waste, like plastic bottles, are a problem for us, but also microplastic, which e.g. was found in drinking water. Microplastics, particles smaller than 5mm, generated by degradation via wave motion and UV radiation, can work their way into the marine food chain and eventually into the human body.

With our project, we want to approach the microplastic problem. On the one hand we want to produce an easy way to detect micro- and nanoplastics in fluids and differ between different polymers. On the other hand, our project should create an easy way to extract them. Magnetic purification seemed to fit, as it doesn’t require any chemicals or elevated equipment.

Currently there are known magnetic bacteria existing, e.g. Magnetpospirillum gryphiswaldense, which thrive in the sediments of freshwater streams or marine sediments in very low oxygen environments. The most fascinating ability of these bacteria is their capability to produce so called magnetosomes, spherical vesicle-like structures of membrane-coated, biomineralized ferrite monocrystals with an approximate diameter of 45 nm. These are aligned by special cytoskeletal proteins inside the cell body to form little compass needles, which allow the bacteria to orient themselves along the earth’s magnetic field.

We want to develop novel fusion proteins embedded into the vesicular membrane of magnetosomes being able to specifically bind certain polymers, for example polypropylene (PP). They are consisting of a transmembrane domain as well as a variable linker domain and a domain for binding the polymer.

Figure 1: Schematic binding of polypropylene (PP) to the magnetosome mebrane (right) via the constructed fusion protein (left).

Figure 1: Schematic binding of polypropylene (PP) to the magnetosome mebrane (right) via the constructed fusion protein (left).

Figure 2: Fluorescent detection of the bound plastic particle with bound fluorescent markers.

Figure 2: Fluorescent detection of the bound plastic particle with bound fluorescent markers.

Novel fusion proteins embedded into the vesicular membrane of magnetosomes can be developed, able to specifically bind certain polymers, for example polypropylene (PP). For detection purposes there is a fluorescent protein marker inside the fusion protein that marks the polymer particle for fluorescent detection.

Our project aims to make the world a little less “plastic”. We don’t want to build up new plastic but to remove the one already present. Join the fight against microplastic and support us by visiting our website. You can ask us anything via e-mail (igem@rwth-aachen.de) and also follow us on Facebook, Instagram and Twitter to stay in touch with us and our journey to the competition in October.

The 2019 Aachen iGEM team

The 2019 Aachen iGEM team

Keynote speaker confirmed: Jakob Schweizer

We are happy to announce Jakob Schweizer as second keynote speaker for the 2019 EUSynBioS symposium!

Jakob Schweizer received his PhD at the Technical University in Dresden under the supervision of Petra Schwille. During that time he held a scholarship of the German Research Foundation and was involved in research coordination as well as public relations. Since 2014 he has been the Scientific Coordinator of MaxSynBio, the Max Planck Research Network for Synthetic Biology.

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Modularity, functionality and rational design are properties that constitute the essence of synthetic biology. However, these properties and goals are not unique to synthetic biology research alone. Jakob Schweizer will draw in his talk the unexpected comparison to the architectural style of Bauhaus, which marks the 100th anniversary of its creation this year. Bauhaus is characteristic for its minimalism and functionalism, and common grounds and boundaries will be discussed in Brno, a city hosting Villa Tugendhat, one of the most prototypical and at the same time outstanding examples of Bauhaus architecture in Europe.

Stay tuned, more speakers to be announced in the next few days! And don’t forget to register to the EuSynBioS 2019 symposium!

Playing Lego with Terpene Biosynthesis

by Laura Drummond

The smell of orange, lemon and grapefruit, the fresh scent of pine trees during a walk in the forest. The taste of mint in toothpastes, the camphor in pain-relief sprays and even the bitter notes of hops in certain types of beer. Terpenes are more present in our lives than we account for, and yet most of us do not know them by name.

 Terpenes are a class of organic compounds, produced by many different types of organisms, but mostly by plants. They are responsible for severalvolatile aroma compounds that we know, but are also involved in the formation larger molecules likecarotenoids and cholesterol, as well as some very important pharmaceuticals like the anti-malarial drug artemisinin and the anti-cancer medicine taxol.

 When it comes to their biosynthesis, terpenoids always form from two universal precursors: IPP (isopentenyl pyrophosphate) and DMAPP (dimethylallyl pyrophosphate), which are isomers from each other. These two molecules have 5 carbon atomseach, and therefore moleculesdownstream normally have a multiple of 5 carbon atoms in their structures. Terpene biosynthesis is modular, with precursors of fixed size and an almost constant count of carbon atoms, which increases in blocks of five as molecules get bigger

Biosynthesis of terpenoids. The pathways have been conceptually separated into four modules. Image:  Vavitsas et al 2018  (CC BY 4.0)

Biosynthesis of terpenoids. The pathways have been conceptually separated into four modules. Image: Vavitsas et al 2018 (CC BY 4.0)

Isopentenyl pyrophosphate (IPP), the universal precursor of Terpenes, and the different precursor molecules that can be formed using a newly discovered methyltransferase.

Isopentenyl pyrophosphate (IPP), the universal precursor of Terpenes, and the different precursor molecules that can be formed using a newly discovered methyltransferase.

In our recent paper, published in ACS synthetic biology, we found a way to challenge this ‘multiples of 5’ rule. We discovered an enzyme, hidden in the genome of Streptomyces monomycini, which is able to add one or two methyl groups (CH3) to the universal precursor of terpenes IPP, creating precursors with 6 or 7 carbon atoms in their structure. The discovery brings an additional piece for the biosynthetical pathway of these compounds, which is highly modular and resembles a game of lego. We also demonstrated the formation of larger molecules, with added methyl groups, showing that natural enzymes from the pathway can accept the different versions of IPP, taking advantage of their promiscuity.

 The findings open new possibilities for the biosynthesis of compounds so far unknown, by the addition of a new piece to the lego-like terpene biosynthetical pathway.

 

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 Laura Drummond is a PhD student at the Industrial Biotechnology Department of DECHEMA Research Institute in Frankfurt, Germany. She has a BSc in Biological Sciences from the University of Sao Paulo and a MSc in Entomology from the Luiz de Queiroz College of Agriculture in Brazil.

Twitter:  @drumm34

Linkedin: https://www.linkedin.com/in/laura-drummond-dechema/

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.