[Closes 27 Nov 2017] PhD on plant gene regulation

PhD available with OpenPlant PI Dr Nicola Patron of the Earlham Institute on design principles for synthetic gene regulation - understanding how cis-regulatory functions are encoded in plant DNA.

Plants are emerging as commercially-relevant production systems for high-value natural products. This requires suites of non-homologous, characterised regulatory elements for applications such as balancing components within a responsive circuit and preventing the build-up of toxic intermediates along a biosynthesis pathway. Plant regulatory sequences are comprised of complex arrangements of protein binding motifs and cis-regulatory elements. Both the primary DNA sequence and secondary DNA structure contribute to regulating gene-expression by recruiting proteins and dictating nucleosome architecture. This project will apply an original synthetic-biology approach to study the relationship between sequence and function utilising comparative genomic approaches to inform the design of synthetic regulatory sequences. This will enable us to understand how cis-regulatory function is encoded in specific DNA sequences. The project will focus on the identification and characterisation of cis-regulatory elements conserved across plants to inform the design of minimal synthetic elements that function across species. Comparative analysis of genome sequences will be used to inform iterative 'design-build-test-learn' cycles in which the function of libraries of designed, synthetic sequences will be analysed. The student will be trained in bioinformatics and comparative genomics analyses, synthetic biology approaches and low and high-throughput plant molecular biology and biotechnology techniques.

More information and application >>

Low cost and open source multi-fluorescence imaging system for teaching and research in biology and bioengineering

Former OpenPlant Fellow Dr Fernan Federici, former OpenPlant PDRA Dr Tim Rudge and colleagues have recently published a pre-print for their low cost and open source multi-fluorescence imaging system for teaching and research in biology and bioengineering, supported by the OpenPlant Fund.

Nuñez, Isaac, Tamara Matute, Roberto Herrera, Juan Keymer, Tim Marzullo, Tim Rudge, and Fernan Federici. "Low cost and open source multi-fluorescence imaging system for teaching and research in biology and bioengineering." bioRxiv (2017): 194324

Examples of images of bacterial colonies and cell-free systems using the microscope. Credit: Federici Lab

Abstract

The advent of easy-to-use open source microcontrollers, off-the-shelf electronics and customizable manufacturing technologies has facilitated the development of inexpensive scientific devices and laboratory equipment. In this study, we describe an imaging system that integrates low-cost and open-source hardware, software and genetic resources. The multi-fluorescence imaging system consists of readily available 470 nm LEDs, a Raspberry Pi camera and a set of filters made with low cost acrylics. This device allows imaging in scales ranging from single colonies to entire plates.

We developed a set of genetic components (e.g. promoters, coding sequences, terminators) and vectors following the standard framework of Golden Gate, which allowed the fabrication of genetic constructs in a combinatorial, low cost and robust manner. In order to provide simultaneous imaging of multiple wavelength signals, we screened a series of long stokes shift fluorescent proteins that could be combined with cyan/green fluorescent proteins. We found CyOFP1, mBeRFP and sfGFP to be the most compatible set for 3-channel fluorescent imaging. We developed open source Python code to operate the hardware to run time-lapse experiments with automated control of illumination and camera and a Python module to analyze data and extract meaningful biological information.

To demonstrate the potential application of this integral system, we tested its performance on a diverse range of imaging assays often used in disciplines such as microbial ecology, microbiology and synthetic biology. We also assessed its potential for STEM teaching in a high school environment, using it to teach biology, hardware design, optics, and programming. Together, these results demonstrate the successful integration of open source hardware, software, genetic resources and customizable manufacturing to obtain a powerful, low cost and robust system for STEM education, scientific research and bioengineering. All the resources developed here are available under open source license

[Closes 30 Nov 2017] GapSummit 2018 open for applications

GapSummit is 'The world’s first global and intergenerational leadership summit in biotechnology' from Global Biotech Revolution and will take place 16-18 April 2018 at St Johns College, Cambridge.

The GapSummit welcomes 100 future bio-leaders (Leaders of Tomorrow) from around the world for a 3-day conference, which aims to "provide the bio-leaders of tomorrow with a comprehensive overview of current and future biotechnology trends and issues, inciting discussion about world challenges that can be met by biotechnological application."

 The GapSummit 2018 will attract more than 60 world leaders and pioneers from the biotech, pharmaceutical & healthcare industry to the University of Cambridge.

APPLY NOW

Deadline 30 Nov 2017

Cafe Synthetique tackles DNA-based Information Storage and DNA Synthesis

Cafe Synthetique on 18 Sep 2017 commanded a full house with plenty of interesting discussion around Pierre Murat's research on DNA-based information storage and Jiahao Huang's work on long chain DNA synthesis.

Pierre Murat from the Department of Chemistry spoke about his research on encoding and decoding synthetic strands of DNA. He presented data to show how he turned (the encoded word) 'Black to 'White', Pierre has also successfully encoded images of Darwin ,Franklin and and Turin! By exploiting differential kinetics of hydrolytic deamination reactions of cytosine and its naturally occurring derivatives, he demonstrated how multiple layers of information can be stored in a single DNA template. He explained how controlled redox reactions allow for interconversion of these DNA-encoded layers of information, encoding a single strand with multiple 'messages'.

Discussion focussed in part, on the challenges of sequencing the complex encoded DNA, including the ultimate test: an outsider successfully decoding a message hidden in DNA from Murat's lab - a challenge many attendees might relish.

Jiahao Huang covered the interesting history of DNA synthesis since it's advent in the 1970's before talking about the exciting work going on at Nuclera Nucleics where heand his colleaguesare developing a next-generation DNA synthesis using engineered terminal deoxynucleotidyl transferases, or TdT. With tehability to synthesise strands tens of bases long already, he hopes to be able to accurately produce long chain DNA strands by the end of this decade, and ultimately whole genomes. Discussion covered, accuracy, large scale production and lead to the inevitable question of cost. With research moving at a rapid pace Jiahao anticipates that a long chain sample will eventually become less than the cost of sending it by FedEx!

OpenPlant Fund supported project publishes on better DNA transfer from Escherichia coli to Bacillus subtilis

Dr Mario Juhas and OpenPlant PI  Dr Jim Ajioka from the Department of Pathology at the University of Cambridge have contributed to creating reliable and efficient systems for the transfer of synthetic DNA between E. coli and B. subtilis, supported by the OpenPlant Fund.

The majority of the good DNA editing techniques have been developed in Escherichia coli; however, Bacillus subtilis is better host for a plethora of synthetic biology and biotechnology applications. 

Using synthetic biology approaches, such as streamlined lambda Red recombineering and Gibson Isothermal Assembly, the team integrated genetic circuits  encoding the lysis genes of bacteriophages MS2, ΦX174 and lambda, the thermosensitive repressor and the T7 RNA polymerase into the E. coli chromosome.

In this system the T7 RNA polymerase regulated by the thermosensitive repressor drives the expression of the phage lysis genes. T7 RNA polymerase significantly increases efficiency of cell lysis and transfer of the plasmid and bacterial artificial chromosome-encoded DNA from the lysed E. coli into B. subtilis. The T7 RNA polymerase-driven inducible cell lysis system is therefore suitable for the efficient cell lysis and transfer of the DNA engineered in E. coli to other naturally competent hosts, such as B. subtilis.

The research obtained support from the SynBio Fund and OpenPlant Fund

The full article can be read here.

Image attribution: Debivort at the English language Wikipedia
This file is licensed under the Creative Commons Attribution-Share Alike 3.0 Unported license.

Cafe Synthetique highlights graduate student work in synthetic biology: algae, arsenic testing and automated labs

Cafe Synthetique this August gave the floor to a talented collection of graduate students working on synthetic biology projects around the University of Cambridge and primarily from OpenPlant Labs. It was an excellent insight into some cutting edge science and how these early career researchers view the future of biological engineering.

Jan Lyczakowski (Department of Biochemistry) from Prof Paul Dupree’s lab described his efforts to engineer the structure of the plant sugar xylan in order to extract more biofuel from woody biomass. By using an enzyme from the plant model organism Arabidopsis thaliana, several times more xylose sugar could be extracted and fermented into ethanol using engineered E.coli bacteria. Jan also brought along some 3D-printed models of xylan to provide a hands-on demonstration of the structure!

Algal synthetic biology featured heavily as Aleix Gorchs Rivera, Stefan Grossfurthner and Patrick Hickland from Prof Alison Smith’s Lab, in the Department of Plant Sciences, presented different approaches to engineering algae to generate valuable products, such as pigments and medicinal compounds.

Patrick’s work focuses on tools to engineer the brown alga Phaeodactylum tricornutum, which is not a common lab organism but has useful features like a rapid growth rate and high accumulation of lipids like omega 3 fatty acids. Specifically, Patrick has engineered an inducible on/off genetic switch in the alga and is now applying it to manipulate metabolic pathways and boost production of useful compounds.

Aleix and Stefan are both working with the more common model alga Chlamydomonas reinhardtii. Aleix presented his work building inducible genetic circuits to express in the algal chloroplast, which is a major site of protein production. He aims to tightly dose expression of interesting metabolic genes and even antibodies. Stefan is constructing a metabolic pathway for engineering and manipulating cytosolic production of sesquiterpenes, an interesting family of compounds including the anti-malarial drug artemisinin. He presented his current progress during the first year of his PhD and future plans.

From eukaryotes to cell-free biochemical systems, Tess Skyrme represented the Sensors Centre for Doctoral Training (Department of Chemical Engineering and Biotechnology), where 12 students have spent the summer designing and prototyping an arsenic biosensor. Their sensor produces glucose oxidase in the presence of arsenic which is detected electrochemically on a device that can send data from remote field locations such as wells in Bangladesh and Nepal, where arsenic contamination has been described as the ‘largest mass poisoning of a population in history’ (WHO, 2002). The team built an arsenic sensitive genetic circuit, tested multiple electrochemistries, and designed an open source potentiometer that is 10% the cost of commercially available options for almost equivalent functionality. They are now focused on integrating the device components ahead of Sensors Day on 20 Oct 2017.

Looking to the future and calling for a revolution in the way that biological experiments are performed, Clayton Rabideau provided an introduction to the current state of the art in machine learning and automation in synthetic biology. His presentation marked the first appearance of Mario Brothers at Cafe Synthetique, with a demonstration of how machine learning over many generations can result in large efficiency gains compared.

Efficiency was also a key driver for the increase in labs moving to automated liquid handling through open source lab robots like OpenTrons, new technologies such as the Labcyte Echo, which is available in Cambridge as part of the OpenPlant Synthetic Biology Centre, and fully automated ‘cloud labs’. However, Clayton also highlighted the ‘reproducibility crisis’ in experimental science and how increased use of machines to minimise human error might help. He ended by predicting that in the coming decades graduate students would spend far less time in the lab. This went down well with an audience whose most automated lab experience so far was reportedly ‘multi-channel pipettes’.

It’s the first time that Cafe Synthetique has featured a full line up of graduate students and we hope to repeat the successful format in the near future. If you are a graduate student working on a synthetic biology related topic and would like to present at the next Cafe Synthetique Grad Talks, get in touch!

New Royal Society Report: Synthetic Biology - does industry get it?

On 8 February 2017, the Royal Society hosted a conference that posed the question Synthetic biology – does industry get it? It brought together nearly 200 experts from academia, industry and government to provide an honest and open appraisal of how industry is using synthetic biology, acknowledging successes and strengths but also looking at what barriers still need to be overcome.

A report from the meeting has now been published, summarising the discussions that took place and the key points raised.

Issues including the global energy challenge, regulation and public acceptance of synthetic biology, and finding the right talent and skills were all raised and great industrial interest in synthetic biology was demonstrated.

In answer to the question, “Does industry get it?”, the Royal Society report that:

"there was a clear sense that industry is very interested in synthetic biology but that there remains a conservativism that holds back its wider implementation. Industry speakers encouraged synthetic biologists to look at solving the unmet needs of industry and demonstrate the benefits that future products will bring. Researchers should avoid the risk of overselling their new and exciting science - there needs to be a balance between ambitious, long-term scientific targets and working within the existing product development lifetimes in industry...Synthetic biology stands on the cusp – as the costs of processes fall, the moment where rapid growth in industrialisation will take place is nearly upon us."

The full report can be read here.

Commentary on a Major Advance in Plastid Transformation

OpenPlant PI Professor Julian Hibberd (Department of Plant Sciences, University of Cambridge) has summarised advances towards efficient plastid transformation in Arabidopsis thaliana as part of a new paper in Plant Physiology

This commentary follows 'Efficient Plastid Transformation in Arabidopsis' reported by Pal Maliga's team in this month's Plant Physiology, which could be regarded as a major advance in plastid transformation. Stable manipulation of the plastid genome of flowering plants was first reported nearly 30 years agoby Svab et al. However, for key species including cereal crops including Arabidopsis (Arabidopsis thaliana), the spectinomycin-based approach using the addition of the aadA gene has proved ineffective.

Hibberd cites Parker et al who showed that ecotypes of Arabidopsis vary in their sensitivity to spectinomycin due to the mutant allele of the nuclear gene ACC2. Its product is targeted to plastids and so provides an alternate to the partially plastid-encoded acetyl-Coenzyme A carboxylase that is inactivated by spectinomycin. Parker et al. proposed that their findings may provide a route to increase efficiency of chloroplast transformation in the Brassicaceae.

Yu et al. (2017) now provide strong support for this conjecture showing that by removing redundancy afforded by ACC2, efficient selection for transplastomic events can be achieved in Arabidopsis.

The next challenge is therefore to identify procedures and ecotypes that facilitate this conversion of transplastomic callus of Arabidopsis into stable and heritable plant material.

Hibberd's full commentary can be read here.

Call for exhibits at Biomaker Fayre 2017

Biomaker Fayre 2017 will include demonstrations of open source biological instruments, lab and field equipment featuring over 40 teams who participated in the 2017 Biomaker Challenge. All others with maker projects related to science and biology are invited to exhibit! We'll have everything from spectrometers for measuring the colour of penguin guano, microfluidics for tissue culture, to ultrasonic systems for measuring plant height and 3D printed modular microscopes.

There'll also be some fantastic talks just before at the Open Technology Workshop. COme and learn about everything from distributed 3D printing in Africa, open hardware in Brazil and universities collaborating with companies to create open technologies in Denmark. 

Want to exhibit?

• Please do! Biomaker Fayre exhibitors can attend the Open Technology Workshop free of charge.
• Every individual exhibitor should register using the esales form under 'concessions'
• Each exhibit must also complete an exhibit registration form

For more information and the schedule take a look at the Open Technology webpage

[Closes 31 Oct 2017] University of Cambridge Lectureship in Synthetic Biology

Applications are invited for a University Lectureship in Synthetic Biology at the University of Cambridge. This is a tenure-track position based in the Department of Engineering and is supported by the School of Biological Sciences (SBS). We particularly encourage applicants who complement current research within Engineering, SBS and across the University, and who are motivated to explore interdisciplinary collaborations.

The successful candidate will have an established DNA-based experimental research program in a topic including, but not limited to:

• Design and engineering of synthetic genetic circuits (both cellular and cell-free)
• Genome engineering
• Biosensing and biological signal processing
• Spatio-temporal gene regulation
• Engineering of multicellular interactions and tissue structure/function

In addition, research may combine theoretical and numerical approaches with experiments. The successful candidate will have, or be expected to develop, a record of world-class research commensurate with the international reputation and top-rank research rating of the Department.

The candidate will be expected to contribute exciting and innovative teaching material to our rapidly growing bioengineering courses in the Engineering curriculum, with teaching and administration accounting for approximately 40% of the role. Teaching responsibilities will include contributing to undergraduate courses, supervising undergraduate projects, examining and supervising postgraduate students.

More information and to apply >>