Our 2020 iGEM team has been selected

We are proud to announce that our 2020 iGEM team has been selected.

We had a large number of applicants and those selected had to present details of their favourite synthetic biology application whilst the interview panel assessed their enthusiasm and the level of research they had done into this concept.

The calibre was exceedingly high, and it wasn’t easy to pick the final team. In the end, 9 students were selected to represent the University of Warwick at the prestigious iGEM Jamboree event which will be held virtually in October 2020. Our final team is comprised of:

  • Grace Goater, 3rd year Biochemistry
  • Aryan Gupta, 2nd year Mathematics, operational Research, Statistics, Economics
  • Jade Oh, 2nd year Biological Sciences
  • Adriana Lopez Gonzalez, 1st year Biomed
  • Tudor Onose, 1st year Biochemistry
  • Valeriia Nadmitova, 2nd year Biomed
  • Adam Jones, 2nd year Computer Science
  • Martin Costa, 2nd year Computer Science
  • Andras Gyori Laszlo, 1st year Biological Sciences

We wish the team the best of luck!

Researchers wake-up DNA from soil bacteria to discover novel acid antibiotic

· A large DNA fragment from a soil bacterium was captured and engineered to be awoken

· The researchers then used to trigger production of a novel natural product, an acid antibiotic, encrypted in that DNA was identified and characterised

· The discovered molecule, Scleric acid, could help combat bacteria and was shown to partially inhibit Mycobacterium tuberculosis, as well as the cancer-associated metabolic enzyme nicotinamide N-methyltransferase (NNMT).

Scleric Acid has been discovered by capturing and engineering a DNA fragment from soil bacteria Streptomyces sclerotialus, and could help fight bacterial infections – by researchers at the School of Life Sciences and Department of Chemistry, University of Warwick.

A team led by Dr Christophe Corre and Dr Manuela Tosin have had published in Chemical Sciencehttps://pubs.rsc.org/en/content/articlepdf/2019/SC/C8SC03814G the characterisation of a new bioactive natural product whose derivatives could be used as antibiotics and help fight infections.

The new molecule was encrypted in a silent cluster of genes in the soil bacterium Streptomyces sclerotialus (isolated in Pune – India) and discovered by turning on an otherwise silent pathway using a combination of bioinformatics analyses, CRISPR/Cas9 gene editing and analytic chemistry instrumentation.

Bioinformatics tools permit to identify proteins encoded in DNA sequences and to predict the role they may play. In the majority of studies aimed to discover new natural products, researchers look for conserved enzymes with homology to known biosynthetic machineries. In this study, conserved regulatory elements associated with biosynthetic genes were targeted. An approach expected to lead to the discovery of natural products assembled by truly novel types of biocatalysts.

The study revealed a structurally new class of natural product but also new biosynthetic enzymes that catalyse unique condensation reactions between the building blocks that make up scleric acid. Such enzymes may find future applications as biocatalysts for the manufacture of high value chemicals.

The expression and manipulation of the cluster of genes of interest was carried out in a secondary organism using quick and efficient CRISPR/Cas9-based gene editing technology. This means that there is no need to optimise a protocol for the engineering of the bacterial species of interest, and this approach can be extended to exploit gene clusters identified in genetically intractable bacteria or even in metagenomes (genetic material recovered directly from environmental samples).

The approach of engineering genetically silent pathways that bacteria are thought to “normally” use to outcompete other micro-organisms could result in the discovery of a wide variety of novel antimicrobial compounds – which could help solve the antibiotic resistance crisis.

The researchers then tested the scleric acid possible antibiotic powers and found that it showed moderate antibacterial activity against Mycobacterium tuberculosis (H37Rv), exhibiting a 32% inhibition on the growth of this strain. The scleric acid also showed inhibitory activity on the cancer associated metabolic enzyme nicotinamide N-methyltransferase (NNMT).

Dr Christophe Corre who is part of the Warwick Integrative Synthetic Biology Centre commented:

“Over the last decade, a combination of technological advances, in particular in DNA sequencing, bioinformatics tool development, microbial genetic engineering and analytical chemistry, has really changed the game. New strategies have been developed to exploit the genomes of bacteria and access a large untapped source of novel molecules with therapeutic potential, in particular to treat infectious diseases.

Using synthetic biology, our study has evidenced that breaking locks at the transcriptional level does trigger the production of truly novel bioactive substances. The next game-changer will be the successful implementation of automation and robotics to characterise the thousands of natural products that remain encrypted at the DNA level.”

Now Recruiting – 4 exciting new roles

WISB are excited to be currently recruiting for three senior technicians, each on a 16 month contract.

Each of the roles will be supporting the research of our Research Career Development Fellows (RCDFs), and span across three different areas of Synthetic Biology.

The deadline to apply is 4th May, with interviews expected to be held a fortnight later. For full information on each of these exciting roles, please visit the following adverts:

www.jobs.ac.uk/job/BJG697/senior-research-technician-88437-048
www.jobs.ac.uk/job/BJG786/senior-research-technician-88438-048
www.jobs.ac.uk/job/BJG787/senior-research-technician-88436-048

We are also recruiting for a postdoctoral fellow to join Emzo de los Santos on a 12 month project to work on cell free in vitro transcription-translation (TX-TL) systems. Full details of this vacancy can be viewed here:

www.jobs.ac.uk/job/BJH752/research-fellow-88435-048

To arrange for an informal discussion about any of the above posts, please do not hesitate to contact wisb@warwick.ac.uk.

Adam Noel speaks to WISB on 04/04/18

WISB are delighted to announce that Adam Noel, from the School of Engineering here at the University of Warwick, will be delivering a Seminar Series lecture from 1-2pm on Wednesday 4 April 2018. Full details of his talk are included below.

If you are interested in attending, please contact wisb@warwick.ac.uk for room details.

Talk title: Using Molecular Communication to Model Biophysical Signal Propagation and Processing

Talk abstract: Molecules are ubiquitiously used in the human body and other biological systems for signaling, control, and regulation. From the perspective of a communications engineer, these molecules carry information. Molecular communication (MC) is an emerging multi-disciplinary field that applies communications engineering tools to molecular signalling. This field seeks to improve our understanding of biological systems and build networks of devices that could operate in fluids. Potential applications in medicine include treating neurological disorders, preventing the growth of cancerous tumors, and mitigating the impact of other illnesses that arise due to ineffective or unintended signaling. Other opportunities include the advancement of environmental monitoring and the design of lab-on-a-chip systems.

This talk will introduce the MC field and highlight our contributions in modeling, analysis, and simulation. In particular, we focus on molecular diffusion, where the molecules of interest propagate randomly within a fluid. We discuss how channel impulse responses can account for physical phenomena, including chemical reactions and bulk fluid flow. We describe and evaluate communication systems that use a simple modulation scheme to transmit sequences of data. We also present an open source simulation platform that we developed for verifying analysis and exploring different environments. Finally, we discuss several areas of on-going and future work to use communications and signal processing tools to improve our understanding of biophysical processes and determine how to control them at a microscopic level.

Drug-producing bacteria possible with synthetic biology breakthrough

Bacteria could be programmed to efficiently produce drugs, thanks to breakthrough research into synthetic biology using engineering principles, from the University of Warwick and the University of Surrey.

Led by the Warwick Integrative Synthetic Biology Centre at Warwick’s School of Engineering and the Faculty of Health and Medical Sciences at the University of Surrey, new research has discovered how to dynamically manage the allocation of essential resources inside engineered cells – advancing the potential of synthetically programming cells to combat disease and produce new drugs.

The researchers have developed a way to efficiently control the distribution of ribosomes – microscopic ‘factories’ inside cells that build proteins that keep the cell alive and functional – to both the synthetic circuit and the host cell.

Synthetic circuitry can be added to cells to enhance them and make them perform bespoke functions – providing vast new possibilities for the future of healthcare and pharmaceuticals, including the potential for cells specially programmed to produce novel antibiotics and other useful compounds.

A cell only has a finite amount of ribosomes, and the synthetic circuit and host cell in which the circuitry is inserted both compete for this limited pool of resources. It is essential that there are enough ribosomes for both, so they can survive, multiply and thrive. Without enough ribosomes, either the circuit will fail, or the cell will die – or both.

Using the engineering principal of a feedback control loop, commonly used in aircraft flight control systems, the researchers have developed and demonstrated a unique system through which ribosomes can be distributed dynamically – therefore, when the synthetic circuit requires more ribosomes to function properly, more will be allocated to it, and less allocated to the host cell, and vice versa.

Declan Bates, Professor of Bioengineering at the University of Warwick’s School of Engineering and Co-Director, Warwick Integrative Synthetic Biology Centre (WISB) commented:

“Synthetic Biology is about making cells easier to engineer so that we can address many of the most important challenges facing us today – from manufacturing new drugs and therapies to finding new biofuels and materials. It’s been hugely exciting in this project to see an engineering idea, developed on a computer, being built in a lab and working inside a living cell. ”

José Jiménez, Lecturer in Synthetic Biology at the University of Surrey’s Faculty of Health and Medical Sciences:

“The ultimate goal of the selective manipulation of cellular functions like the one carried out in this project is to understand fundamental principles of biology itself. By learning about how cells operate and testing the constraints under which they evolve, we can come up with ways of engineering cells more efficiently for a wide range of applications in biotechnology”

Ribosomes live inside cells, and construct proteins when required for a cellular function. When a cell needs protein, the nucleus creates mRNA, which is sent to the ribosomes – which then synthesise the essential proteins by bonding the correct amino acids together in a chain.

Based on an original idea arising from discussions between Alexander Darlington, a PhD candidate at the University of Warwick, and Dr. Jiménez, the theory of dynamically allocating resources in cells was tested and analysed with mathematical modelling at Warwick, and then built and demonstrated in the laboratory at the University of Surrey.

Notes to editors:

The research, ‘Dynamic allocation of orthogonal ribosomes facilitates uncoupling of co-expressed genes’, is published Open Access in Nature Communications.

doi:10.1038/s41467-018-02898-6

It is authored by Alexander P. S. Darlington, Juhyun Kim, José I. Jiménez & Declan G. Bates.

Our iGEM team has been selected

We are proud to announce that our 2018 iGEM team has been selected.

We had the largest number of applicants to date, from which 20 were selected to attend an afternoon of interviews. Each student had to present details of their favourite synthetic biology application whilst the interview panel assessed their enthusiasm and the level of research they had done into this concept.

The calibre was exceedingly high, and it wasn’t easy to pick the final team. In the end, 11 students were selected to represent the University of Warwick at the prestigious iGEM Jamboree event which will be held in Boston in October 2018. Our final team is comprised of:

  • Alizah Khalid, 2nd year Biomedical Sciences
  • Gurpreet Dhaliwal, 1st Biochemistry
  • Jack Lawrence, 2nd Medical Microbiology
  • James O’Brien, 3rd Biomedical Sciences
  • Janvi Ahuja, 2nd Biomedical Sciences
  • Jonny Whiteside, 2nd Biochemistry
  • June One, 2nd Law
  • Kurt Hill, 1st Computer Science
  • Laura Mansfield, 1st Life Sciences and Global and Sustainable Development
  • Olivor Holman, 2nd Biological Sciences
  • Rhys Evans, 2nd Medical Microbiology

We wish the team the best of luck, and know that they will have a great summer working on their iGEM project and will make the University proud when they present in Boston.

Design and Engineering of Synthetic Biosystems in Spetses, Greece

WISB are proud to announce their participation in the organisation of a FEBS Advanced Course.

Entitled Design and Engineering of Synthetic Biosystems, the course will run from 9-17 September in the island of Spetses in Greece.

This course will be of most benefit to PhD students, and early career postdoctoral fellows. The course will be comprised of lectures, seminars, discussion groups and tutorials. The course registration fee will cover the admin fees, accommodation, and the majority of meals. There are a number of travel grants available which will cover course registration and travel expenses.

For more information, please visit the FEBS website.  If you would like to have an informal discussion about the course, please email Dr Corinne Hanlon on wisb@warwick.ac.uk.

Francisco J. Navarro speaks to WISB on 21/03/18

WISB are delighted to announce that Francisco J. Navarro, from the Department of Plant Sciences at the University of Cambridge, will be delivering a Seminar Series lecture at 1pm on Wednesday 21 March 2018. Full details of his talk are included below.

If you are interested in attending, please contact wisb@warwick.ac.uk for room details.

Talk title: miRNA-mediated regulation of synthetic gene circuits in the green alga Chlamydomonas reinhardtii

Talk abstract: microRNAs (miRNAs), small RNA molecules of 20–24 nts, have a number of features that make them ideal tools to regulate gene expression — small size, flexible design, target predictability and action at a late stage of the gene expression pipeline. miRNAs confer robustness to gene networks and are involved in the fine-tuning of gene expression, functions which are desirable to implement in plant synthetic gene networks. The use of miRNAs in synthetic circuits requires a good understanding of their quantitative parameters and mode of action, which is, however, hindered by the complexity of natural systems. Here we apply a synthetic biology approach to characterize miRNA-mediated gene expression regulation in the unicellular green alga Chlamydomonas reinhardtii. Using fluorescent reporter systems we quantify miRNA-mediated repression activity, study the mode of action of miRNAs, and identify synthetic miRNAs with different repression activities. We utilize this characterization to design and implement miRNA-mediated synthetic gene circuits in the alga. These results, which are revealing key features of Chlamydomonas miRNA pathway, will be used as a proof-of-concept for the engineering of miRNA-based gene circuits in higher plants.

Simon Moore on 22/02/18: Cell-Free – Transcription, Translation and Biosynthesis

Dr Simon Moore will speak to WISB, and the wider Life Sciences community, on Thursday 22nd February about his research on cell-free-transcription, translation and biosynthesis. Simon is a Faculty Research Fellow in Paul Freemont’s group at Imperial College London. An abstract of his talk is included below.

More information on Simon’s research an be found on his ResearchGate profile.

If you are interested in attending, please contact wisb@warick.ac.uk.

Talk title: Cell-Free – Transcription, Translation and Biosynthesis

Talk abstract: Cell-free (or in vitro transcription-translation) synthetic biology is a fast evolving “test-bed” technology for studying genetic circuit design, biosensors, metabolic engineering and the development of minimal cell systems. This talk will discuss the current opportunities within cell-free, along with presenting the recent development of two new bacterial cell-free systems for high-throughput screening applications.

Firstly, using an industrially relevent Bacillus strain that specialises in recombinant protein production, I will demonstrate an automated experimental and modelling workflow to create a “blueprint” of gene expression dynamics and resource (energy, ribosomes) competition in cell-free. This cell-free system is also scalable for rapid and automated screening of ~100-1000s of library DNA parts and promoter systems (inducible and constitutive) that are native to the host. This approach is potentially expandable to a whole range of cell-free systems (e.g. mammalian, bacterial, fungal) for high-throughput screening applications in biotechnology.

Finally, the second part of the talk, will introduce and discuss the recent development of a Streptomyces cell-free system for the expression of high G+C (%) genes and it’s potential utility for studying Streptomyces genetic tools and natural product biosynthesis.

 

Georg Fritz on 28/02/18: Engineering orthogonal synthetic timer circuits in bacteria

Dr Georg Fritz (SYNMIKRO, University of Marburg, Germany) will be speaking at the WISB Seminar Series on Wednesday 28th February from 12-1pm in the School of Life Sciences.

If you would like to attend, please contact wisb@warwick.ac.uk for location details. An abstract of Georg’s talk is as follows:

The rational design of synthetic circuits is often impeded by cross-reactions between circuit components and physiological processes within the heterologous host. In our work seek to overcome these restrictions by using extracytoplasmic function σ factors (ECFs), which represent ideal orthogonal regulators because of their high promoter specificity. After evaluating several heterologous ECF switches in E. coli and B. subtilis, computational modelling allows us to predict cascades with multiple ECFs. These “autonomous timer circuits” activate a series of target genes with defined time delays, which we find in excellent agreement with experimental data. Our results not only serve as a proof of concept for the application of ECFs as organism-independent building blocks in synthetic biology, but could also be used in biotechnological applications, e.g. to introduce a timing hierarchy in the expression of biosynthetic pathway components.