PAPER: Strategy to improve the conversion of plant biomass to sugars for bioenergy

New OpenPlant paper from the Dupree Lab, University of Cambridge. The publication in Biotechnology for Biofuels describes work to improve processing of softwood to biofuels using a synthetic biology strategy to express and assay conifer cell wall synthesis enzymes.


Removal of glucuronic acid from xylan is a strategy to improve the conversion of plant biomass to sugars for bioenergy.

Lyczakowski, J.J., Wicher, K.B., Terrett, O.M., Faria-Blanc, N., Yu, X., Brown, D., Krogh, K.B.R.M., Dupree, P., and Busse-Wicher, M. (2017).

Biotechnology for Biofuels 10:224: https://doi.org/10.1186/s13068-017-0902-1

Abstract

Background: Plant lignocellulosic biomass can be a source of fermentable sugars for the production of second generation biofuels and biochemicals. The recalcitrance of this plant material is one of the major obstacles in its conversion into sugars. Biomass is primarily composed of secondary cell walls, which is made of cellulose, hemicelluloses and lignin. Xylan, a hemicellulose, binds to the cellulose microfibril and is hypothesised to form an interface between lignin and cellulose. Both softwood and hardwood xylan carry glucuronic acid side branches. As xylan branching may be important for biomass recalcitrance and softwood is an abundant, non-food competing, source of biomass it is important to investigate how conifer xylan is synthesised.

Results: Here, we show using Arabidopsis gux mutant biomass that removal of glucuronosyl substitutions of xylan can allow 30% more glucose and over 700% more xylose to be released during saccharification. Ethanol yields obtained through enzymatic saccharification and fermentation of gux biomass were double those obtained for non-mutant material. Our analysis of additional xylan branching mutants demonstrates that absence of GlcA is unique in conferring the reduced recalcitrance phenotype. As in hardwoods, conifer xylan is branched with GlcA. We use transcriptomic analysis to identify conifer enzymes that might be responsible for addition of GlcA branches onto xylan in industrially important softwood. Using a combination of in vitro and in vivo activity assays, we demonstrate that a white spruce (Picea glauca) gene, PgGUX, encodes an active glucuronosyl transferase. Glucuronic acid introduced by PgGUX reduces the sugar release of Arabidopsis gux mutant biomass to wild-type levels indicating that it can fulfil the same biological function as native glucuronosylation.

Conclusion: Removal of glucuronic acid from xylan results in the largest increase in release of fermentable sugars from Arabidopsis plants that grow to the wild-type size. Additionally, plant material used in this work did not undergo any chemical pretreatment, and thus increased monosaccharide release from gux biomass can be achieved without the use of environmentally hazardous chemical pretreatment procedures. Therefore, the identification of a gymnosperm enzyme, likely to be responsible for softwood xylan glucuronosylation, provides a mutagenesis target for genetically improved forestry trees.

[Closes 11 Oct 2017] Knowledge Frontiers: International Interdisciplinary Research Projects

The British Academy is inviting proposals from UK-based researchers across all disciplines within the social sciences and humanities to develop international interdisciplinary research projects with development impact, in collaboration with colleagues from the natural, engineering and/or medical sciences.

Aims

The purpose of each project will be to develop new ideas and methods to bear on existing international challenges and to deliver policy-relevant outputs which could potentially improve the welfare of people in developing countries. Proposals that creatively tackle cultural, public and/or policy controversies, or explore how such controversies have been understood and responded to in the past, would be particularly welcome. Such controversies might include, but need not be limited to, changing climate, movements across borders, socio-biological problems, artificial intelligence, medical humanities, people and infrastructures, and responses to or understanding of diseases and pathogens.

The complexities of global change and the proliferation of diverse communities of knowledge, practice and intelligence highlight the necessity of collaborative engagement between communities of practice, disciplines, capacities and borders. The British Academy is keen to support and work with proposals that strengthen understanding of challenges in this context and engage with questions concerning the relationship between expertise, public understanding and policy delivery. We are interested in projects of interdisciplinary nature that examine encounters between academic, professional and lay knowledge, and how valid knowledge, knowledge associations and evidence are built and developed, communicated and disseminated, and the factors which can serve as barriers to this in different political or cultural settings.

Eligibility requirements

The lead applicant must be based at a UK university or research institute, and be of postdoctoral or above status (or have equivalent research experience). International co-applicants, and in particular co-applicants from OECD DAC countries, are strongly encouraged.

The British Academy will require applicants to demonstrate that their proposals are ODA eligible. ODA eligibility is an essential criterion – projects will only be deemed eligible for funding if they can demonstrate that they satisfy ODA eligibility criteria.

Value and Duration

Awards are of one-year in duration and are available for up to £50,000. Funding can be used to support research and/or clerical assistance; research expenses and consumables; travel and subsistence; and networking, meeting and conference costs. Awards are not funded on a full economic costs basis, with contributions to overheads an ineligible cost. 

Application Process

Application deadline: Wednesday 11 October 2017 (17.00 UK Time)

Read more >>

[Closes 31 Sep 2017] PhD Studentship in sex chromosome evolution in liverworts

Evolution of sex chromosomes is well-studied in organisms in which sex is expressed in the diploid phase. In such organisms the lack of recombination and the asymmetry in haploidy are assumed to lead to the progressive decay of the Y chromosome. In organisms in which sex is expressed in the haploid phase both U and V chromosomes are equally devoid of recombination and show no asymmetry in recombination suppression. This provides a unique opportunity to tease apart the effect of this two factors on the evolutionary trajectory of sex chromosomes. We are using a combination of classical genetic and comparative genomic approaches to test hypotheses concerning sex chromosome evolution in haploid dioecy using liverworts as a suitable model system (Marchantia polymorpha, Preissia quadrata and many more).

The goal of this project is to (1) develop a new methodology for capturing and sequencing complete sex chromosomes in plant model systems and (2) to reconstruct their evolutionary history both at the gene and structural levels. Therefore, this position involves molecular laboratory work to develop and optimize capturing and sequencing protocols; bioinformatics work to analyze and interpret the generated next- generation sequencing data; and evolutionary and functional genetic analysis of the evolution of sex chromosomes in the model plant Marchantia polymorpha and other liverwort species. This project is aimed at addressing one of the fundamental questions of evolutionary biology, the genetic makeup of sex chromosomes in a haploid plant model organism, via developing a new cutting-edge method for third-generation sequencing.

The student will work 18 months at University of Zurich, Switzerland. The other 18 months at BaseClear, The Netherlands. Peter Szovenyi, University of Zurich; Prof. Elena Conti, University of Zurich, Prof. Michael Lenhard, University of Potsdam; Dr. Walter Pirovano, Dr. Adalberto Costessi and Dr. Daniël Duijsings, BaseClear BV, The Netherlands will jointly supervise the successful candidate. 

This is project is conducted in the framework of PlantHUB. PlantHUB is funded by the H2020 PROGRAMME Marie Curie Actions – People, Initial Training Networks (ITN).

Advocacy Science Explained - using biotechnology as a case study

Cambridge researcher Ksenia Gerasimova unravels how advocacy science has changed political discourse in science, and the general perception of the role of science in contemporary society.

Biotechnology is an extreme example of how science has had to confront issues such as the place and role of science in society, the need for scientists to communicate and advocate their research to the public and policy-makers, secure funding and address the ethical concerns relating to their research. 

This paper discusses the use of term ‘advocacy science’ which is communication of science that goes beyond simple reporting of scientific findings, using two case studies in biotechnology.

  • The first, is the 'Puzstai case', when on the documentary, 'World in Action' in 1998, Dr Arpad Puzstai from the Rowett Institute of Research in Scotland raised his concerns over GM foods, in regards to a study conducted at the institute aiming to transfer a snowdrop plant gene to potato (Puzstai 1991). The UK media reacted in force. This sparked the debate over the use of GM crops, and also provoked another about the very way scientific experiments are conducted, interpreted and communicated. 
  • The second case study is the Seralini Case, when in 2012 a publication by Professor Gilles-Éric Séralini, at the University of Caen, France, on the 'Long term toxicity of a Roundup herbicide and a Roundup-tolerant genetically modified maize' catalysed the discussion not only amongst the media, but also within the scientific community on where the moral aspects of science and scientific communication stands.

Over a relatively short period of time 1998-2012 a large change in the perception of science had happened: it was now seen in a postmodernist style as a social construct, including the natural scientists themselves.

The paper argues that advocacy science should be used to distinguish the engagement of modern civil society organisations to interpret scientific knowledge for their lobbying. It illustrates how this new communicative process has changed not only the politics surrounding science, but our perception of the role of science in contemporary society. It cites OpenPlant as an example of where generic lower-level tools that are largely free of IP constraints can be freely shared to promote innovation in plant synthetic biology (OpenPlant 2016).

Gerasimova suggests that the controversies in the GM debate have contributed not just to policy-making for GM crops, but also to the way biotechnological science, and possibly even science in general, is communicated and perceived. 

 The full article can be read at: 
Gerasimova, K., 2017. Advocacy Science: Explaining the Term with Case Studies from Biotechnology. Science and Engineering Ethics, pp.1-23.

Biomaker Challenge - building collaborations through low-cost instrumentation

Biomaker Challenge is a four-month programme challenging interdisciplinary teams to build low-cost sensors and instruments for biology. The programme aims to facilitate exchange between the biological and physical sciences, engineering, and humanities for the development of open source biological instrumentation using commodity electronics and DIY approaches.

image_mini (1).png

The inaugural 2017 cohort comprises 130 participants working in 41 teams on biological and biomedical devices, instruments, and sensors.  Participating teams received a Biomaker Toolkit and a discretionary budget for additional sensors, components, consumables, and mechanical fabrication worth up to £1000.

Teams of all sizes were considered for the grant and range from an individual to twelve people. Interdisciplinarity within participating teams is prioritised and although most participants are students or staff at the University of Cambridge, John Innes Centre or the Earlham Institute, external team members are welcome and included designers from the Royal College of Art, computer scientists from ARM, local artists, makers, and entrepreneurs.

During the challenge, we offer assistance and support providing components and access to prototyping facilities in Cambridge such as Cambridge Makespace and the Media Studio on the Cambridge Biomedical Campus. We also run periodic technical workshops and meetups to encourage teams to interact and help share skills and ideas. Participating teams will document a full set of assembly/fabrication instructions, images, and a list of components used, which are made publicly accessible via GitHub. This will enable others to replicate and build on their work for their own research questions. The challenge culminates on 21 October 2017 in a public exhibit, the Biomaker Fayre, where participants will demonstrate their creations and prizes will be awarded for especially creative and enabling projects.

The Challenge will repeat in 2018 and we look forward to seeing the projects develop with a new cohort of participants to further increase access to low-cost, open access biological tools and technologies.


Example Projects

Real-Time monitoring of cell proliferation

An absorbance sensor that can be used inside a cell culture incubator for real-time monitoring of culture medium pH and cell density. The system is able to automatically transmit this data to an email server for remote monitoring of cultured cells.

Microfluidic Turntable for molecular diagnostic testing

An Arduino controlled turntable with a stroboscope for disk visualisation on screen and optical detection for absorbance and fluorescence measurements. The disc, fabricated using a laser cutter and paper plotter, is rotated by an Arduino controlled motor. Fluid actuation is also controlled by Arduino, changing the rotation direction and revolutions per second to achieve pumping, mixing and separation.

A programmable staging mount, and an imaging platform for a microfluidics based conditioned learning hub for motile bacterial cells.

By developing a maze traversal challenge, different scenarios for chemotactic bacterial colonies to employ their decision-making machinery and navigate through the maze will be assessed. This may lead to an understanding of cognition, memory and learning in bacterial colonies.

 

 

 

Plant-made synthetic polio vaccine

New paper from Lomonossoff lab, John Innes Centre. The publication in Nature Communications describes work funded by the World Health Organisation to produce a new polio vaccine in plants, using the HyperTrans transient expression system. It is hoped that this new vaccine will be a move towards global eradication of polio. The publication was covered by JIC News and the BBC.


Plant-made polio type 3 stabilized VLPs—a candidate synthetic polio vaccine

Marsian, J., Fox, H., Bahar, M.W., Kotecha, A., Fry, E.E., Stuart, D.I., Macadam, A.J., Rowlands, D.J., & Lomonossoff, G.P. (2017)

Nature Communications 8, Article number: 245 https://doi.org/10.1038/s41467-017-00090-w

Abstract

Poliovirus (PV) is the causative agent of poliomyelitis, a crippling human disease known since antiquity. PV occurs in two distinct antigenic forms, D and C, of which only the D form elicits a robust neutralizing response. Developing a synthetically produced stabilized virus-like particle (sVLP)-based vaccine with D antigenicity, without the drawbacks of current vaccines, will be a major step towards the final eradication of poliovirus. Such a sVLP would retain the native antigenic conformation and the repetitive structure of the original virus particle, but lack infectious genomic material. In this study, we report the production of synthetically stabilized PV VLPs in plants. Mice carrying the gene for the human PV receptor are protected from wild-type PV when immunized with the plant-made PV sVLPs. Structural analysis of the stabilized mutant at 3.6 Å resolution by cryo-electron microscopy and single-particle reconstruction reveals a structure almost indistinguishable from wild-type PV3.

BoomTown Fair, August 2017

Blog post written by Emma McKechnie-Welsch, and reproduced with permission from The SAW Trust. Original blog post can be found here: http://sawtrust.org/news/boomtown-festival-august-2017

Science tent at Kidztown

Science tent at Kidztown

BoomTown Fair is an annual music and arts festival held in Winchester. It attracts up to 60,000 people a year. The festival hosts a wide range of performances across its many stages, providing visually impressive themed areas on-site.

This is also the case with Kidztown, the diverse and interactive family area. OpenPlant and the SAW Trust were key contributors to the Kidztown science tent. Children here were introduced to different natural plant-based products in a fun and engaging way. This included a carefully devised potion-making, craft and spell-writing stand.

The stand, titled "Marvellous Medicines," revolved around our periodic table of natural products. The children were tasked with making a magical potion, picking just one component from each block of the periodic table for their ingredients. The blue block contributed a plant material that would provide the colour pigmentation for the potion, including the magical element of colour change in different pH solutions. The red block contained plants with appealing scents, extracted as essential oils, to give the potion a delightful smell. Finally, the yellow block contained citrus fruit. The citric acid in this can be used to observe the colour change.

Periodic table of plants

Periodic table of plants

Making the Potions

Once the children had selected their ingredients, they ground up the blue item (either red cabbage, berries, turmeric or selected flowers) using a pestle and mortar. They then practised using pipettes, adding 75 percent ethanol to extract the pigment. This was transferred to their potion flask. They next added the essential oil corresponding to their red item and 1 millilitre of bicarbonate of soda solution to observe the first colour change. Last of all, 35 millilitres of citric acid solution was added to create the final colour of their potion. It was explained that citric acid was the compound in citrus fruit that made it taste so sharp.

Whilst a slight fizz was observed upon adding the citric acid, due to it reacting with the bicarbonate of soda, only a very small amount of the bicarb was present. The final step involved adding a green slime of more bicarb mixed with washing up liquid, which caused the potions to fizz over and release the essential oil smell. If the kids wanted an extra colourful potion they also added food colouring gel.

Magical ingredients

Magical ingredients

Colourful results

Colourful results

Making potions

Making potions

Marvellous Medicine's Art and Writing

Artist Molly Barrett helped the children create their own artistic potion bottle, cutting out bottle shapes from cardboard and sticking dried plant products to them. Our writer Ali Pritchard asked the children to think about what they wanted their potion to do, and they wrote a spell to cast over their potion for it to work. This was written on acetate and stuck to their art creation. 

Marvellous Medicines team members

Marvellous Medicines team members

Throughout, the children learned about a plant’s ability to make different compounds that define their features such as colour, scent and taste. They extracted the colour pigment themselves and used other natural extracts to complete their potions, observing how we can use things that plants make for our own products. The older children also learned about pH and colour indicators, a classic chemistry practical they will no doubt carry out in secondary school. A further use for plants was discovered in the art stand: the plant materials could be used as 3D elements to decorate the potion bottles.

The finished potions

The finished potions

The children let their creativity run wild by imagining what their natural product potion could achieve. Whilst compounds produced by plants may not be able to turn glitter into gold or the sea into Ribena, hopefully the children took away the idea that many of the compounds produced within plants can be used in ways they previously hadn't thought about. Not least, the children had lots of fun exploring ideas around magical plant extracts and many of the children returned to the stand later on.

Marvellous Medicines couldn’t have been a success without the hard-working team, who over three days helped the children through all the tasks. A big thank you goes to the team and to BoomTown for having us!

The Marvellous Medicines Team

The Marvellous Medicines Team

Cambridge Consultant Synthetic Biology PhD Studentship

Cambridge Consultants is building an exciting new business in biotechnology, particularly synthetic biology. They’re working to bring together biology, chemistry and engineering to design and build engineered biological systems. As part of this mission, they're looking for a bright, motivated PhD student to join the team on an internship.

No deadline has been given but the advert was posted in Aug 2017.

With a strong background in biochemistry or molecular biology, the successful applicant will work alongside our scientists and engineers to apply their scientific skills and knowledge to our synthetic biology projects.  They’ll learn how new technology is applied in a business context and the challenges this presents.  

This is a three-month internship with flexible timing.

More information >>

[Closes 1 Sep 2017] Plant Synthetic Biology Assistant/Associate Professor (University of Nebraska)

Plant Synthetic Biology Assistant/Associate Professor The University of Nebraska-Lincoln (UNL) is committed to conducting world-class research in plant biochemistry and has recently secured a $20 million Experimental Program to Stimulate Competitive Research (EPSCoR) Grant from the NSF to establish the Center for Root and Rhizobiome Innovation (CRRI). Reflecting the institutional commitment to building infrastructure in plant biochemistry, UNL is seeking applicants for nine-month (academic year) tenure-leading Assistant Professor or Associate Professor faculty position (80% research and 20% teaching) in the Department of Biochemistry and the Center for Plant Science Innovation.

They will address the development and application of synthetic biology tools to address questions central to plant biology that contribute to crop productivity and/or quality.

Required qualifications include a PhD or equivalent in biochemistry, biology, molecular biology, plant physiology or related field; a minimum of two years of postdoctoral experience; and a strong record of original research as evidenced by peer- reviewed publications. For Assistant Professor, the incumbent is expected to develop an internationally recognized research program that attracts federal, commodity, international foundation, and/or industry funding leading to research results published in refereed scientific journals and presented at professional meetings. Applicants at the Associate Professor levels must have an externally supported research program and/or sufficient private sector experience, with publication, patent, and presentation outcomes demonstrating sustained and recognized research productivity. The incumbent will broadly address the development of synthetic biology tools, which may include but are not limited to those involving genome editing, gene stacking, and/or RNA-based control of gene expression and apply these tools for studies of photosynthesis, central carbon metabolism, specialized metabolism or other biochemical or biological processes that lead to improved crop germplasm. The ability to apply computational methods for use of large data sets in synthetic biology tool development is also desired. The university offers state of the art proteomics and metabolomics core facilities in the Center for Biotechnology and high-speed computing resources in the Holland Computing Center. Extensive field facilities, state-of-the-art image-based phenotyping instrumentation, breeding resources, and crop transformation core capacity are available to support translational research. This position is part of the Institute of Agriculture and Natural Resources initiative in Stress Biology, which offers a highly collaborative environment to develop focused research programs linked with modern biochemical methodologies, metabolic engineering, metabolomics, genomics, and computational approaches. A competitive start-up package and appropriate laboratory and office space will be offered.

The incumbent will contribute to the teaching mission of the College of Agricultural Sciences and Natural Resources and in particular will develop and teach undergraduate and graduate courses in the biochemistry core curriculum. It is expected that the incumbent will contribute to recruitment, retention and placement activities; incorporation of outcomes assessment; engagement in instructional improvement; mentoring undergraduate and graduate students; and serve on department, college, and UNL committees as appropriate.

To learn more about the University of Nebraska, the Department of Biochemistry and the Center for Plant Science Innovation see http://biochem.unl.edu ; http://www.unl.edu/psi/ .

How to Apply

To view details of the position and make application, go to http://employment.unl.edu Search for position F_170058. Click on “Apply to this job.”

Postdoctoral Research Fellow on engineering synthetic phage (Jaramillo Lab, Warwick University)

The goal of the Jaramillo lab is to achieve proof of concept for synthetic phages within the next 3 years. By working at the interface of molecular biology, combinatorial optimisation, microfluidics, directed evolution and 3D printing it is hoped that reaching this goal will accelerate more synthetic biology research globally thus enhancing our ability to combat diseases of the future.

There is no closing date listed, but the advert was posted in Aug 2017

From Warwick University:

“Superbugs…these are our babies…now they have body piercings and anger” - House, TV Show

According to the World Health Organisation antibiotic resistance is one of the biggest threats to global health, food security, and development today. The prevalent use of modern antibiotics over the last century has led to a bacterial arms race with increasingly potent infections proving more difficult to treat as each year passes. As the efficacy of our current armoury of antibiotics wanes, hospital stays lengthen, medical costs rise and without urgent action we will soon enter a post-antibiotic world where common infections will kill once again. While there are some new antibiotics in development, none of them are expected to be effective against the most dangerous forms of antibiotic-resistant bacteria of the future.

Is there a possible response that could safeguard humanity? Professor Alfonso Jaramillo thinks so and his lab at the University of Warwick is working hard to provide such a solution. It is a multidisciplinary lab that develops novel automated methodologies for design optimisation using computers, viruses or living cells for use in Phage Therapy. The ambition is the eventual development of synthetic phages, powerful antimicrobials which if their work proves successful will herald a new age in the fight against bacterium. Progress of the lab since 2013 has been steady with the foundations already laid of new technologies (computational and experimental) for the engineering of biomolecules. The key current focus is on the creation of automated algorithms that enable directed evolution in support of the difficult design phase of Synthetic Biology, by developing a general methodology for the de novo engineering of synthetic RNA parts and circuits it is hoped they will work robustly as targeted in a given cellular context.

The goal of the lab is to achieve proof of concept within the next 3 years. By working at the interface of molecular biology, combinatorial optimisation, microfluidics, directed evolution and 3D printing it is hoped that reaching this goal will accelerate more synthetic biology research globally thus enhancing our ability to combat diseases of the future.

This is where you come in, as a Postdoctoral Research Fellow we need your expertise to help build the lab’s research capability. You will form part of a high profile international team with labs in Warwick and ISSB in France. Your contribution to the lab’s body of knowledge in support of the goal of reaching proof of concept will have a direct impact on one of the most urgent health threats facing humanity.

More information >> [PDF] 

[Closes 22 Aug 2017] Research Associate position on open hardware for science (University of Bath)

From University of Bath:

Open source hardware could bring about a step change in science and medicine, by making high quality instruments more widely available and easier to customise. We are looking for a talented researcher with (or soon to be awarded) a PhD in Physics, Engineering, or a related discipline, to work as part of the "Open Lab Instrumentation" project that includes the Universities of Bath and Cambridge as well as our partners STICLab in Tanzania.

Salary: Starting from £32,004, rising to £38,183
Placed On: Monday 24 July 2017
Closing Date: Tuesday 22 August 2017
Interview Date: To be confirmed
Reference: SF5079

This project will enable high quality open-source instrumentation, by characterising and improving the mechanical properties of 3D printed mechanisms, then using these optimised structures, together with readily available electronic and optical components, as building blocks for microscopes, spectrometers, micromanipulators and more. Our first open instrument, the OpenFlexure Microscope, has already been reproduced by a number of groups, and tested in applications from malaria diagnostics to water quality monitoring.

You will build an understanding of how the small-scale structure of 3D printed parts (the "toolpath") affects their properties, then use this understanding to create improved toolpaths that result in stronger or more flexible parts.  This will involve both simulations and lab-based measurements, as well as adapting open-source software tools to generate the optimised toolpaths.  You will then go on to create designs for instrumentation using those optimisations, as well as contributing to software tools that allow others to do the same.  Good programming skills are essential, and experience in instrumentation design, mechanical simulation, and/or 3D printing is highly desirable.   As our goal is open-source hardware, we will contribute to various open source projects as well as starting new ones, and experience of open or collaborative development of either software or hardware would be particularly valuable.

You will be based within the Centre for Photonics and Photonic Materials in the Department of Physics.  This post is funded by an EPSRC project that is part of the Global Challenges Research Fund, announced by the UK Government to support cutting-edge research that addresses the challenges faced by developing countries.  In keeping with the international remit of this funding, there will be opportunities to travel to meet our Tanzanian partners, and to work with the end-users of our new instruments. 

Physics at the University of Bath is a research-led Department, ranked highly in the UK in the latest Research Excellence Framework, and the University recently attained a Gold rating in the Teaching Excellence Framework. Both the Department and the University are committed to providing a supportive and inclusive working environment, with an active Athena Swan programme and opportunities for researchers to receive training, mentorship, and career development.

Informal enquiries are encouraged, and should be directed to Dr. Richard Bowman (r.w.bowman@bath.ac.uk). 

More information >>

PAPER: Platform for rapid gram-scale production of small molecules in planta

New OpenPlant paper from the Osbourn Lab, John Innes Centre. The publication in Metabolic Engineering describes a platform developed for production of gram-scale quantities of small molecules in plants in just a few weeks, using the HyperTrans transient expression system.


A translational synthetic biology platform for rapid access to gram-scale quantities of novel drug-like molecules

Reed, J., Stephenson, M.J., Miettinen, K., Brouwer, B., Leveau, A., Brett, P., Goss, R.J.M., Goossens, A., O’Connell, M.A., and Osbourn, A (2017)

Metabolic Engineering 42:185-193: https://doi.org/10.1016/j.ymben.2017.06.012

Highlights

  • Transient plant expression technology provides rapid access to diverse triterpenes.
  • Gram-scale quantities of purified triterpene can be generated.
  • Agro-infiltration can be exploited for quick and easy combinatorial biosynthesis.
  • Bespoke known and new-to-nature compounds can be generated.
  • The platform allows isolation of analogs for structure-activity investigations.

Abstract

Plants are an excellent source of drug leads. However availability is limited by access to source species, low abundance and recalcitrance to chemical synthesis. Although plant genomics is yielding a wealth of genes for natural product biosynthesis, the translation of this genetic information into small molecules for evaluation as drug leads represents a major bottleneck. For example, the yeast platform for artemisinic acid production is estimated to have taken >150 person years to develop. Here we demonstrate the power of plant transient transfection technology for rapid, scalable biosynthesis and isolation of triterpenes, one of the largest and most structurally diverse families of plant natural products. Using pathway engineering and improved agro-infiltration methodology we are able to generate gram-scale quantities of purified triterpene in just a few weeks. In contrast to heterologous expression in microbes, this system does not depend on re-engineering of the host. We next exploit agro-infection for quick and easy combinatorial biosynthesis without the need for generation of multi-gene constructs, so affording an easy entrée to suites of molecules, some new-to-nature, that are recalcitrant to chemical synthesis. We use this platform to purify a suite of bespoke triterpene analogs and demonstrate differences in anti-proliferative and anti-inflammatory activity in bioassays, providing proof of concept of this system for accessing and evaluating medicinally important bioactives. Together with new genome mining algorithms for plant pathway discovery and advances in plant synthetic biology, this advance provides new routes to synthesize and access previously inaccessible natural products and analogs and has the potential to reinvigorate drug discovery pipelines.

UK SynBio Start-Up Survey published showing thriving East of England ecosystem

SynbiCITE have published the first survey of the UK synthetic biology start-up ecosystem, highlighting the changing sources of innovation and entrepreneurship at work in the sector from a macro-level perspective.

The report covers activity between 2000 and 2016 in research and development, technology transfer, industrial sectors, financing and investors. Its key finding were:

  • The UK produced more than 146 synthetic biology start-ups between 2000 and 2016.
  • More than half (54%) of new start-ups are tech transfer start- ups,
  • Synthetic biology start-up activity is concentrated in the South-East, East of England and London (67%). With Oxford, Cambridge and London Universities producing a cluster of activity nucleating in and around London. 
  • Synthetic biology start-up companies have raised over £620m of public (£56m) and private (£564m) investment in the UK since 2010. 

Dr. Stephen Chambers, CEO of SynbiCITE, commented that “Confirming the arrival of a new innovation ecosystem demands evidence: proof that variables ranging from investment, pipeline infrastructure, to talent and education are established and stable. We believe the industry has reached a critical mass of companies, showing a healthy churn of attrition and creation. Roughly 76% of all the start-ups founded in the survey period are still active and with the continuation of an effective national strategy in the future, this ecosystem will undoubtedly thrive, creating jobs and wealth while sustaining the UK’s leading role in the field.”

East of England emerged as the region with the highest number of synthetic biology start-ups after London, with spin-offs concentrated around the OpenPlant partner locations of Cambridge and Norwich. 

Read More >>

Download Report [PDF, 4MB]

 

Plant Science SAW projects at Tunstead primary School

Guest blog from Emma McKechnie-Welsch, a PhD student from the John Innes Centre who spent three months doing an internship in Science Engagement with OpenPlant and the SAW Trust.

 

Plant Science SAW projects at Tunstead primary School

Arabidopsis apical meristem. Image by Emma McKechnie-Welsch

Arabidopsis apical meristem. Image by Emma McKechnie-Welsch

My name is Emma and I am a PhD student working in the Cell and Developmental Biology department at the John Innes Centre. My research looks at genes functioning to facilitate controlled plant growth and development from the shoot apical meristem in Professor Robert Sablowski’s research group. My PhD funding from the BBSRC includes a three month work placement and I was keen to gain experience in science communication and outreach so arranged a joint placement with OpenPlant and the SAW trust.

On my placement I had the opportunity to design two SAW projects to discuss science relevant to my research with primary school children at Tunstead primary school. For the year 1/2 class I worked with writer Julia Webb and artist Lara Nicole and the aim was to get children thinking about the functions of different parts of a plant. For the year 5/6 class I was worked with writer Mike O’Driscoll and artist Chris Hann with a day themed around plant evolution.

 

We used scientific images at the start of the day to catalyse inquisitiveness about the science we were going to explore, and provide inspiration for the poetry and art sessions.

 

Practical Science with Year 1/2

Build a plant game, played with year 1/2 class

Build a plant game, played with year 1/2 class

To start off the lesson we played a “build a plant” game to get more familiar with the main parts of a plant, their function, and what plants use from their environment to grow. Each child also put a cut flower in coloured water to think about the use of the stem. Then the children were given a selection of fruit and vegetables and asked to decide what part of the plant each came from. They were given a flower to look more closely at the reproductive parts and think about how seeds are formed by pollination. Finally, they looked at different types of seeds in a seed kit and we discussed the different types of seed dispersal tactics plants use.

 

Practical Science with Year 5/6

The children dissected plants to look up close at the reproductive parts under the microscope.

The children dissected plants to look up close at the reproductive parts under the microscope.

We began by guessing the number of different plant species on earth and the children suggested why plants are useful. In groups, they were given cards representing each component of photosynthesis and had to arrange them to think about the process. We covered pollination and its importance for increasing genetic variation.

The children dissected plants to look up close at the reproductive parts under the microscope. I covered different types of seed dispersal and the importance of varying environmental conditions for evolution. Then children carried out DNA extraction from strawberries after learning a bit about what DNA was and how important it was in controlling the appearance of the plant, with a single mutation in a gene coding region potentially greatly changing this. Following on from DNA extraction there was a game to match the numbers of genes to different organisms.

 

 

After the morning science sessions the children had poetry and art sessions based on the content. Here are some poems and images from the Year 5/6 group (age 10/11):

Poem 1.png
Yr 6 art work.jpg
Poem 1.png

 

The Year 1/2 children (age 4/5) wrote poems as if they were a seed growing up, and made flower hand puppets after designing a flower:

sock puppets.jpg

The children really engaged with the scientific learning aspect of the day which was great. Lots of the children thought about the questions I asked to the classes and gave insightful answers, as well as wanting to ask questions throughout the lesson/ activities. When asked about their favourite part of the day, at least half the children listed specific sections of the science morning.

The poems produced by the year 5/6 children really showcased the children’s interest in understanding genetics and how growth and development of organisms are controlled. The younger children were enthusiastic about looking at different types of seeds, bringing back different types they had found in their school grounds at break time to show me. It was great for them to think about the different stages of growth a plant goes through from seed to eventually producing a flower, including difficulties different environmental conditions could cause, while writing their poems.

The children were really excited about getting to do an afternoon of art although the activities designed weren’t quite as expected. The art didn’t centre around drawing on paper but producing 3D art pieces. The younger children gave lots of personality to their individual hand puppets and used them to help communicate their poetry whilst the older children focused on the scientific pictures provided and gave interpretations of pollen and seed dispersal, as well as the protective mechanism of the cactus.

From this experience, I could see how integration of science with writing and art can help children associate science more closely with creative thought, rather than a regimented, inflexible learning process, which makes the subject inaccessible to some children. The teachers were impressed with the pieces the children managed to produce and the level of thought about scientific processes they reached, which I think was largely down to the different approach to education SAW days take.

[Closes 31 Aug 2017] Call for Fellows at CRI Research

Information from the website of the Centre Recherches Interdisciplinaires (CRI): https://cri-paris.org 

The CRI collaboratory is recruiting fellows to join their adventure. They are inviting applications for three types of fellows: short (3-6 months), long (1-3 years) and core (5 years): https://cri-paris.org/research/call-for-fellows/


The CRI is broadening its research activities, creating a collaboratory at the crossroads across the life, learning, and digital sciences.

We are developing an open, collaborative research program to tackle the world’s health and education challenges, focusing on the following broad topics, amenable to bridge foundational research and societal impact:

  • Open health – from data-rich research to development of frugal software and hardware solutions.
  • Open learning – from understanding learning to human-machine paradigms
  • Open synthetic and systems biology – from foundational understanding of living systems to open biotech and open pharma solutions.
  • Open transitions – from tracing past major transitions to understanding and shaping current digital transition.
  • Open phronesis – tackling ethical challenges of our time.

The Collaboratory will host short (3-6 months), long (1-3 years) and core (5 years) research fellows alongside with their affiliated postdocs and PhD students. They will be accompanied by associate faculty members from France and abroad that will take part in the selection and mentoring the incoming fellows and students. Anyone capable of carrying an autonomous research project, from young graduates to established researchers (including sabbaticals) is eligible to apply to become a CRI Research Fellow.  We expect a gradual recruitment build-up to reach a 60-70 strong cohort within our dedicated building at the historical heart of Paris (the Marais) that will open its doors within a year. This 6500m2 building will include state-of-the-art wet lab space, makerspace, pedagogic facilities and studio apartments for young researchers.

[Closes 9 Aug 2017] DNA Foundry, Science and Technology Lead

Applications are invited for a DNA Foundry, Science and Technology Lead to join the Engineering Biology Group at the Earlham Institute. Using start-of-the-art laboratory automation and synthetic biology approaches, the Foundry has automated nanoscale pipelines for (i) part-based assembly and bacterial transformation, (ii) quality control of assemblies and (iii) delivery of constructs to chassis organisms. The mission of the Foundry is to bring these capabilities to bear on research in academia and industry. The post holder will establish and manage synthetic biology workflows at the Earlham DNA Foundry. This will include working with automation specialists and technical assistants to develop and execute protocols in DNA assembly, biosynthesis and genome engineering. In addition, they will engage and communicate with researchers in academia and industry to promote the mission of the Earlham Foundry and to establish and develop new collaborations. The ideal candidate will possess a PhD in Molecular Biology, Biotechnology, Synthetic Biology or a related subject. They will have an in depth understanding of molecular biology laboratory techniques and experience of collaborating with internal and external stakeholders on large scale projects. They must possess excellent communication and interpersonal skills. This position is open to applicant of all nationalities.

All applications must be made through the portal link: http://www.earlham.ac.uk/dna-foundry-science-and-technology-lead

Contact: nicola.patron@earlham.ac.uk

OpenPlant and the OpenMTA feature in 'Learning by Sharing' at SB 7.0

Prof Jim Haseloff, Dr Nicola Patron and BioBricks Foundation Legal Director Dr Linda Kahl who pioneers the OpenMTA initiative with which OpenPlant is collaborating, all presented in the 'Learning by Sharing' session at SB 7.0 in Singapore, 13-16 June 2017.

The videos of all talks are now online at the BioBricks Vimeo site.

Prof Jim Haseloff (Director, OpenPlant at University of Cambridge)

Dr Nicola Patron (Earlham Institute)

Dr Linda Kahl (BioBricks Foundation)

OpenPlant researchers advance a translational synthetic biology platform for rapid access to new drug-like molecules

Researchers in Prof Anne Osbourn's lab at the John Innes Centre, including Prof Osbourn and OpenPlant PDRA Dr Michael Stephenson, have published a new paper detailing their advances in rapidly creating and purifying gram-scale quantities of natural products that were previously not possible to synthesise. This has the potential to reinvigorate drug discovery pipelines by opening up whole regions of chemical diversity for testing and production of potentially medicinally important molecules.

OAlogo.png

Reed, J., Stephenson, M.J., Miettinen, K., Brouwer, B., Leveau, A., Brett, P., Goss, R.J., Goossens, A., O’Connell, M.A. and Osbourn, A., 2017. A translational synthetic biology platform for rapid access to gram-scale quantities of novel drug-like moleculesMetabolic Engineering. DOI: 10.1016/j.ymben.2017.06.012

Fig 2 from paper: Generation of gram quantities of triterpene using vacuum infiltration a, Vacuum infiltration of N. benthamiana plants. Plants are retained by a bespoke holder, inverted into a bath containing 10 L of A. tumefaciens suspension, and a vacuum applied. Upon release of the vacuum the infiltration process is complete. b, GFP expression in leaves from a vacuum-infiltrated plant 5 days after infiltration (leaves arranged from top left to bottom right in descending order of their height on the plant). The youngest leaves (top left) were formed post-infiltration. c, β-Amyrin purified from vacuum-infiltrated plants following transient expression.

Fig 2 from paper: Generation of gram quantities of triterpene using vacuum infiltration a, Vacuum infiltration of N. benthamiana plants. Plants are retained by a bespoke holder, inverted into a bath containing 10 L of A. tumefaciens suspension, and a vacuum applied. Upon release of the vacuum the infiltration process is complete. b, GFP expression in leaves from a vacuum-infiltrated plant 5 days after infiltration (leaves arranged from top left to bottom right in descending order of their height on the plant). The youngest leaves (top left) were formed post-infiltration. c, β-Amyrin purified from vacuum-infiltrated plants following transient expression.

Abstract

Plants are an excellent source of drug leads. However availability is limited by access to source species, low abundance and recalcitrance to chemical synthesis. Although plant genomics is yielding a wealth of genes for natural product biosynthesis, the translation of this genetic information into small molecules for evaluation as drug leads represents a major bottleneck. For example, the yeast platform for artemisinic acid production is estimated to have taken >150 person years to develop. Here we demonstrate the power of plant transient transfection technology for rapid, scalable biosynthesis and isolation of triterpenes, one of the largest and most structurally diverse families of plant natural products. Using pathway engineering and improved agro-infiltration methodology we are able to generate gram-scale quantities of purified triterpene in just a few weeks. In contrast to heterologous expression in microbes, this system does not depend on re-engineering of the host. We next exploit agro-infection for quick and easy combinatorial biosynthesis without the need for generation of multi-gene constructs, so affording an easy entrée to suites of molecules, some new-to-nature, that are recalcitrant to chemical synthesis. We use this platform to purify a suite of bespoke triterpene analogs and demonstrate differences in anti-proliferative and anti-inflammatory activity in bioassays, providing proof of concept of this system for accessing and evaluating medicinally important bioactives. Together with new genome mining algorithms for plant pathway discovery and advances in plant synthetic biology, this advance provides new routes to synthesize and access previously inaccessible natural products and analogs and has the potential to reinvigorate drug discovery pipelines.

 

 

Twenty-nine Biomaker Challenge projects funded plus extra deadline for proposals - 21 July 2017

Twenty-nine Biomaker Challenge projects were funded by the SRI, OpenPlant and CamBridgSens covering a huge range of biology and engineering tasks from cell-free synthetic biology to clinical devices to lab automation solutions. Due to late interest, we have added a later deadline of 21 July.

Starting in this summer for the first time, the Biomaker Challenge is a four-month programme challenging interdisciplinary teams to build low-cost sensors and instruments for biology. From colorimeters to microfluidics and beyond, we were looking for frugal, open source and DIY approaches to biological experiments and we found them! The proposals contained a rich set of interdisciplinary project ideas from across the University of Cambridge and Norwich Research Park, with many external collaborators from local industry, the Royal College of Art and further afield.

 The 29 awardees have now been announced (see full list below) and will shortly be documented on GitHub and the Biomaker.org website, where some proposals are already online.

Biomaker Challenge Coordinator Kyata Chihbalabala has recently joined the SRI for ten weeks to manage the programme and arrange training and meetups. The Biomaker Toolkits are now being distributed so watch this space for events coming soon!

Apply by 21 July for Biomaker Challenge Round Two!

Due to a rush of late interest, we have decided to open another round. You still have an opportunity to apply for a Biomaker Toolkit (worth £250) and £750 additional support for your biological instrumentation project.

Find out more about how to apply >>

Acknowledgements

Judging Panel: Dr Emre Ozer (ARM Ltd), Dr Stephanie Reichel (CRUK Cambridge Institute), Dr Dan MacLean (Earlham Institute), Prof Jim Haseloff (Department of Plant Sciences, University of Cambridge), Dr Alexandre Kabla (Engineering Department, University of Cambridge), Dr Oliver Hadeler (Chemical Engineering and Biotechnology, University of Cambridge).

Sponsors: ARM Ltd, New England Biolabs

 

The Funded Projects

  1. A cell-free sensor platform for the quantification of arsenic concentrations in drinking water.
  2. A Device for Real-Time Monitoring of Protein Synthesis.
  3. A low cost reusable microfluidic device for the detection of antibiotic resistant genes in bacteria isolated from patient samples.
  4. A low cost, point-of- care device to measure blood haemoglobin levels, using calorimetry and infrared spectroscopy.
  5. A low-cost colorimeter for accurate detection of colour changes in medical diagnostic tests
  6. A low-cost, pressurized liquid chromatography system for protein purification
  7. A microdroplet incubator to establish 3D organoids cultures from oesophageal adenocarcinoma.
  8. A sensor to improve the accuracy of stereotactic brain biopsies for the diagnosis of brain tumours
  9. An artificial habitat to investigate Boquila trifoliata mimicry
  10. Cheap Do-It- Yourself Small Volume UV Spectrometer for Nucleic Acid and Protein Quantitation
  11. Detecting alterations in ionic concentrations associated with different cellular states
  12. Detecting pathogens in sewage sludge
  13. Developing a self-regulating control system for intravenous drug administration -- using aminoglycosides as an example
  14. Development of an anti-TFF3 functionalized surface to capture of Barrett’s oesophagus cells
  15. DIY bioacoustics
  16. Field portable colorimeter
  17. Functional membrane-based integrated biosensing devices for detection and quantitation of specific nucleic acids and other biomolecules
  18. Handheld syringe pump with heating element
  19. KNOW-FLOW: A low-cost programmable blood flow system
  20. Low Cost Wearable Sensors Strain Sensors for illness identification via Gait, Posture and muscle usage
  21. Low-Cost Multispectral Imagery for UAV-based Vegetation Monitoring
  22. Macrophotography of fern gametophytes using a DIY focus stacking system.
  23. Microfluidic Turntable for molecular diagnostic testing
  24. OptoFlow: Optical flow rate measurement for microfluidics
  25. Puzzle-solving Bacterial Pet: Imaging Platform for Microfluidics-based Reinforced Learning with Motile Bacterial Cells
  26. Remote Environment Controller for Experiments in Extreme Environments
  27. Sci-Fi Cam
  28. Ultrasonic Plant Height System for High- Throughput Plant Phenotyping
  29. Real-Time monitoring of cell proliferation

 

Biomaker Challenge is sponsored by BBSRC/EPSRC through OpenPlant Synthetic Biology Research Centre (www.openplant.org) and the University of Cambridge Research Policy Committee through the Synthetic Biology Strategic Research Initiative (www.synbio.cam.ac.uk) and the Sensors Strategic Research Network (www.sensors.cam.ac.uk).