Dr Georg Fritz: 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.

Now open: applications for iGEM

WISB is excited to announce that we are now accepting applications for next year’s iGEM team who will represent the University of Warwick at the competition in Boston in November 2018.

We are seeking enthusiastic, creative, and motivated undergraduate students, with a problem-solving attitude, from all across the University to form the most multi-disciplinary iGEM team Warwick has ever seen! This is the first time that applications have been open to students from all disciplines.

The team will not only conduct research into Synthetic Biology, but will be responsible for engaging with the general public, putting together a business plan, designing a website, developing code, and investigating the human practices associated with Synthetic Biology.

To apply, or to come to a talk on 17th January to hear more information, visit warwick.ac.uk/igem. The deadline for applications is 28th January.

This year’s team will have to dig deep if they are to meet the same levels of determination that was shown by last year’s group, Blueprint 361. Last year’s group was comprised of the following members and the team went to great lengths to engage the general public about Synthetic Biology. They ran a highly successful school day where local Year 12 students got to experience Synthetic Biology at university.

  • Amy Moore (Life Sciences)
  • Balint Vidos (Engineering)
  • Ben Cox (Engineering)
  • Elsita Jungkurth (Life Sciences)
  • Jack Lawrence (Life Sciences)
  • Omar Shafi (Engineering)
  • Robert Richardson (Chemistry)
  • Sophie Clarke (Engineering)
  • Wendy Wei (Life Sciences)
  • Zahid Kadir (Engineering)

SynBioCDT now open for applications!

The EPSRC & BBSRC Synthetic Biology Centre for Doctoral Training (SynBioCDT) is a 4-year doctoral programme that offers training in the new field of Synthetic Biology, the “Engineering of Biology”. This centre is a collaboration between the Universities of Oxford, Bristol and Warwick.

Students from a wide range of academic backgrounds are encouraged to apply such Engineering, Biology, Biochemistry, Physics, Plant Sciences, Chemistry, Statistics, Mathematics and Computing. The deadline is 12 January 2018.

Applications can be made through any of the three collaborating institutions, where they will be admitted for graduate study. All students will spend most of their first year in Oxford and will then rejoin their home institution to complete their doctorate.

For more information, including funding details, please visit www.synbio-cdt.ac.uk

Information on the individual centres is listed on their websites:

 

The ‘lost 99%’ of microplastic ocean pollutants can now be identified

Estimates of how much plastic is in the ocean are not accurately represented as microplastics are hard to identify.

A team of researchers from the University of Warwick, led by WISB member Dr Joseph Christie-Oleza, has devised a new way to identify what is known as the “lost 99%” of plastic particles in the world’s oceans.

Microplastics are pieces of plastic less than 5 millimetres in size and are the most common type of pollutant in the oceans. They break down from larger chunks and are not readily visible so they are usually left out when researchers analyse ocean waters, notes a report by the Independent. That means 99% of all the plastics in the ocean actually go unaccounted for.

The Warwick team has come up with a kind of dye that lights up plastics, making it easier for analysts to spot even the smallest piece of plastic in ocean waters. The scientists then proceeded to check waters using their new method and found a lot more particles than what was previously estimated.

“Using this method, a huge series of samples can be viewed and analysed very quickly, to obtain large amounts of data on the quantities of small microplastics in seawater or, effectively, in any environmental sample,” said University of Warwick researcher Gabriel Erni-Cassola.

The study has been published in Environmental Science & Technology, a peer reviewed journal.

Before this method was devised, the only way for researchers to analyse microplastics in sea water was to physically pick them out, one at a time. Now, the dye will settle on plastics and they can then be placed under a microscope where they will light up. The entire process can be automated.

“Have we found the lost 99% of missing plastic in surface oceans? Obviously this method needs to be implemented in future scientific surveys to confirm our preliminary findings,” said co-author Dr Joseph Christie-Oleza.

The researchers were able to easily identify samples and find plastics that are no wider than a human hair. Even at that size, they pose a threat to the environment, especially if they are ingested by marine animals.

Scientists are yet to fully understand the effects plastics have on marine life. What they do know is that microplastics are eaten by animals in the ocean and that when it gets absorbed by their bodies it can lead to starvation as well as cause changes in several bodily and behavioural functions.

This approach to identifying plastics is an attempt to better measure the extent of pollution only. “It is important to understand how plastic waste behaves in the environment to correctly assess future policies,” said Dr Christie-Oleza. The next step would be to attempt to clean up the oceans.

“Shared resources by the numbers” from Andras Gyorgy (23 November)

WISB is delighted to announce that Andras Gyrogy, Assistant Professor at NYU Abu Dhabi, will be coming to deliver a talk on Thursday 23rd November. Andras is part of the NetBio Group. Please email wisb@warwick.ac.uk if you would like to attend.

Talk abstract

Without accounting for the limited availability of shared cellular resources, the standard model of gene expression fails to reliably predict experimental data obtained both in vivo and in vitro. To overcome this limitation, we developed a dynamical model of gene expression explicitly modeling competition for scarce resources. In addition to accurately describing the experimental data, this model only depends on a handful of easily identifiable parameters with clear physical interpretation. Based on this model, we characterized the combinations of protein concentrations that are simultaneously realizable with shared resources, matching experimental data both in vitro and in vivo. Application examples of these results include the design of optimal experiments for parts characterization, the characterization of parts whose expression is not accessible through direct measurements, and the standardization of cell-free extracts. Finally, some ongoing efforts will be discussed within the context of biological controller design to address some of the issues caused by the scarcity of shared resources.

Biography

Andras completed his PhD with Domitilla Del Vecchio at MIT (collaborating with Jim Collins and Ron Weiss), during which time he visited Richard Murray at Caltech to work with their TX-TL system. He then spent 1.5 years as a postdoc with Murat Arcak at UC Berkeley (collaborating with Adam Arkin). Currently, he is an Assistant Professor at NYU Abu Dhabi blending wetlab experiments with theoretical analysis on (bio)networks. Building upon the above influences, Andras’s work focuses on network dynamics and synthetic biology (e.g., optimal experiment design, system identification, model order reduction). What he is especially interested in is developing quantitative tools and standardized probes for predicting mRNA and protein expression precisely both in vitro using cell-free extracts and in vivo.

 

Apply now for a PhD starting in October 2018

Applications can be made to the SynBio CDT programme for PhDs starting in October 2018. The 4-year studentships cover UK/EU Tuition Fees in full and pay an annual stipend. The next application deadline is 24th November 2017.

The SynBioCDT draws upon the breadth and depth of multidisciplinary expertise within the research environment at the Universities of Oxford, Bristol and Warwick to offer comprehensive training in the design and engineering of biologically based parts, devices and systems as well as the re-design of existing, natural biological systems across all scales from molecules to organisms.

Students from a wide range of backgrounds are encouraged to apply.

For more details see the SynBioCDT website.

Reduced models of circadian clocks: Dr Ozgur Akman (8 November)

Dr Ozgur Akman is a Senior Lecturer in the Mathematics department at the University of Exeter, and will be visiting WISB as part of our seminar series on Wednesday 8th November.

Ozgur will speak about his research which could lead to the reverse-engineering of large-scale biochemical networks. If you would like to attend, please email wisb@warwick.ac.uk.

The full abstract for Ozgur’s talk is as follows:

The gene networks that comprise the circadian clock modulate biological function across a range of scales, from gene expression to performance and adaptive behaviour. In recent years, computational models of these networks based on differential equations have become useful tools for quantifying the complex regulatory relationships underlying the clock’s oscillatory dynamics. However, optimising the large parameter sets characteristic of these models places intense demands on both computational and experimental resources, limiting the scope of this approach. In this talk, a complementary approach based on combining Boolean logic with evolutionary optimisation will be introduced that dramatically reduces the parametrisation and computational load, making the state and parameter spaces more tractable. Through the construction of Boolean models fitted to both synthetic and experimental time courses, it will be shown that logic models can reproduce the complex responses to environmental inputs generated by more detailed differential equation formulations. In particular, it will be demonstrated that logic models have sufficient predictive power to identify optimal regulatory structures from experimental data. This suggests that the capacity of logic models to provide a computationally efficient representation of system behaviour could facilitate the reverse-engineering of large-scale biochemical networks.

More information on Ozgur’s research. 

Successful meet at WISB’s International Workshop

The WISB International Workshop ran from Tuesday 19th – Thursday 21st September 2017 and was hosted at the picturesque Palazzo Pesaro Papafava, the University of Warwick’s conference facility in Venice.

Over the course of the three days, delegates experienced many informative and insightful talks from both WISB members and invited international experts in Synthetic Biology. There were many discussions had over the banquet meal on Wednesday evening!

Special thanks are to be extended to Dr Sarah Bennett who coordinated the entire workshop, and to those who travelled great distances to join us.

To see some highlights from the workshop, search Twitter for #WISBinVenice

Prof Barbara Ann Halkier: Pathway and transport engineering

Visiting WISB from the DynaMo Center in the Department for Plant and Environmental Sciences at the University of Copenhagen on Wednesday 1st November, Prof Barbara Ann Halkier will be speaking about pathway and transport engineering when using glucosinolates as case study.

If you are interested in attending Barbara’s talk, please email wisb@warwick.ac.uk.

Abstract of Barbara’s talk:

Cruciferous vegetables are unique in synthesizing the natural products glucosinolates. Substantial attention is given to particularly the glucosinolate glucoraphanin that is present in broccoli, as it is generally thought to be the major bioactive compound associated with the cancer-preventive effects of broccoli. The health-promoting effects have resulted in a strong desire to increase the intake of glucoraphanin. Establishment of a microbial production of glucoraphanin will provide a stable, rich source of this compound and enable intake of well-defined doses. Using transient expression in tobacco, we have shown the feasibility of engineering in a heterologous plant the seven genes pathway of indole glucosinolate, and the 12 genes pathway of the glucosinolate glucoraphanin. In yeast and E. coli, we have successfully engineered the benzyl glucosinolate pathways. However, engineering of the 12 genes glucoraphanin pathway poses challenges. Latest development in our goal towards microbial production of glucoraphanin will be discussed. Transport engineering is receiving increased attention as a novel means to control accumulation of specific metabolites. In Brassica crops, glucosinolates are anti-nutritional factors that reduce the nutritional value of the high-quality protein-rich seed meal that is a byproduct in the oil production. Recently, we showed that by mutating two glucosinolate transporters it was possible to eliminate glucosinolates from seeds of the model plant Arabidopsis. As an example of translational biology, we have successfully translated the gtr loss-of-function phenotype from the Arabidopsis model plant to Brassica crops, – a novel and potentially generic transport engineering approach for reducing seed glucosinolate content in other oilseed crops.

Nour-Eldin HH et al. (2017) Reduction of antinutritional glucosinolates in Brassica oilseeds by mutation of genes encoding transporters. Nature Biotechnology, 35, 377

Further information about Barbara’s research can be found here. 

Dr Ross Anderson at next seminar series

Visiting WISB from the University of Bristol, Dr Ross Anderson will be speaking on Wednesday 11th October at 1pm (MRI room) about the design of new proteins and enzymes and how this remains one of the great challenges in biochemistry.

Ross will explain how our fundamental understanding of both the nature of protein as a material and the principles of enzymatic catalysis is currently being tested and remoulded.

Dr Munehiro Asally will be hosting lunch with Ross beforehand for those interested in speaking with him.

Full details of Ross’s talk can be found in the Seminar Series.