Coupling droplet microfluidics with Mass Spectrometry

Emily Kempa: With the number of variants in a combinatorial library regularly exceeding 105 entities, SYNBIOCHEM Manchester are looking for new high throughput technologies for screening these variations for useful mutations to take forward into the next round of development. Although the Sphere Fluidics droplet platform and the FACS system are regularly utilised in the department for this use, their inherent downfall is the reliance upon the target compound to be fluorescent. To overcome this, a label-free approach in which the Sphere Fluidics droplet platform will be modified and coupled to a mass spectrometer has been devised.

This project has begun by coupling a droplet microfluidic chip with mass spectrometry through the insertion of a stainless steel emitter into a chip, and integrating this chip with the Agilent 6560 IM Q-TOF Mass Spectrometer. Droplets (~2 nL in size) are generated in the chip at a rate of 5 Hz and are introduced into the MS almost immediately with each droplet being detected as a distinct peak in the total ion chromatogram. Each peak in this chromatogram allows us to obtain a mass spectrum for each droplet, something that will be come of up-most importance when filling droplets with individual variants from the library or even monitoring reaction progress.

Discover our Research on YouTube

Watch our new University of Manchester Chemistry videos on YouTube! HERE

Demystifying the science behind our research papers, these videos provide a real world view of how important these discoveries are for day to day life.

These include: Finding new routes to replacement molecules for oil using yeast; Developing new routes to cheaper, better drugs by pairing man-made synthesis with natural enzymes; and harnessing the power of enzymes to make useful molecules for pharmaceuticals, polymers and plastics using alcohol.


How robots could solve the antibiotics production crisis

The World Health Organisation, has highlighted a lack of new antibiotics in development which is leading to a crisis in antibiotic production and our ability to tackle infections. However, cutting-edge technology gives us a chink of hope in what could otherwise be seen as an intractable problem says Eriko Takano, Professor of Synthetic Biology at The University of Manchester. SYNBIOCHEM is combining the strengths of biology with the power of engineering to find new ways to deal with this problem.

Full article here

iGEM 2017 Manchester success at the Giant Jamboree!

Manchester iGEM 2017 Awarded Gold at the Giant Jamboree! : This year our team of undergraduate students from the University of Manchester and Manchester Metropolitan University are working on a project that aims to engineer a bacterium that can take up and store increased levels of phosphate through micro-compartments.

Tackling the problem of phosporus through phosphostore – a system which could sequester and store high levels of Phosphate.  “We may be able to substitute nuclear power for coal power, and plastics for wood, and yeast for meat, and friendliness for isolation – but for phosphorus there is neither substitution nor replacement – Issac Asimov’s “Life’s bottleneck”

Breakthrough in pharmaceuticals production with new enzyme discovery

Scientists have discovered a new enzyme that will make a drug used to treat Parkinson’s disease cheaper and quicker to produce. Researchers at the Universities of Manchester and York found the enzyme in Aspergillus oryzae, a kind of fungus used for making soy sauce. The discovery, ‘A reductive aminase from Aspergillus oryzae’ was published in Nature Chemistry.

The enzyme’s greatest impact could be in a class of medications called monoamine oxidase (MAO) inhibitors. One such example of this kind of drug is Rasagiline, which helps Parkinson sufferers by increasing a substance in the brain that affects motor function. These substances help reduce the involuntary tremors that are associated with the condition. The medicine works in both early and advanced Parkinson’s, and is especially useful in dealing with non-motor symptoms of the condition, like fatigue.

The team, led by Professor Nick Turner, Professor of Chemical Biology from the Manchester Institute of Biotechnology (MIB), have identified a new biocatalyst (RedAm) that accelerates a process called reductive amination.“This is a very exciting discovery from both a chemistry and pharmaceutical perspective. It is the first enzyme of its kind that has these properties and has the potential to improve the production of this and other important drugs.” Professor Nick Turner

New species of yeast could help beer brewers reach new heights

Researchers at the University of Manchester have discovered a new species of yeast that could help brewers create better lager. Working in collaboration with the National Collection of Yeast Cultures (NCYC), the team say it is a new of  member of the Saccharomyces family and is closely related to the familiar brewers’ and bakers’ yeast.

However, this new species was found at altitude, growing more than 1000 metres above sea level on an oak tree in Saint Auban, in the foothills of the French Alps. To survive at this altitude, the yeast has developed an ability to tolerate colder conditions than most other known strains of Saccharomyces yeasts.

Professor Daniela Delneri, from the Manchester Institute of Biotechnology at The University of Manchester, said: “This ability is of interest to brewers, as lagers rely on yeasts that thrive in the cold; it also open the opportunity to create arrays of novel yeast hybrids with improved biotechnological traits.” Yeasts also play a major role in many industrial biotechnology applications that rely on their fermentation, and a yeast that operates at lower temperatures opens up potential new applications in this field.

Synthetic Biology UK 2017

27-28th November 2017, Manchester Conference Centre, UK. The SynBio UK conference aims to showcase UK Synthetic Biology research and to create a focal point for the community, embracing its diversity and fostering its growth and its engagement with society. Held in the vibrant city of Manchester, where scientists first split the atom, and next door to the Manchester Institute of Biotechnology which is home to SYNBIOCHEM, we will have some focus towards chemicals and industrial biotechnology at this year’s meeting.

Abstract submission and early bird registration deadline Friday 29th  September 2017.  All attendees, particularly researchers in the early stages of their career, are invited to submit a poster abstract for consideration as an oral communication.

C3 Bio-Technologies Ltd

A spin out company, C3 Bio-Technologies Ltd, was incorporated to utilise synthetic biology to facilitate the production of propane.  The company seeks to develop an economically-sustainable manufacturing process for full-scale bio-propane production and brings together two long-standing specialists from Biotechnology research, Professor Nigel Scrutton director of the Manchester Institute of Biotechnology and SYNBIOCHEM, and the LPG industry, Michael Smith  director of Pressure Tech Transport Services Ltd a specialist regional supplier of LPG. New website 

Research paper on the development of synthetic pathways for renewable biosynthesis of propane can be found here.

SpeedyGenes gene synthesis method

DNAbluecode2A new chapter in Methods Mol. Biol. (Currin et al, 2017. Vol 1472, 63-78) describes our SpeedyGenes method that allows the assembly of DNA sequences with fewer errors and its use to encode extensive, statistically designed sequence variation at any position in the sequence to generate diverse yet accurate variant libraries.  We also describe the integrated use of GeneGenie to design DNA and oligonucleotide sequences, followed by the procedure for assembling these accurately and efficiently using SpeedyGenes. These methods provide useful tools for synthetic biology and biotechnology where gene synthesis is utilised to assemble any desired DNA sequence, which can then be incorporated into novel parts and pathways.

Microbial cell factories for the production of high-value pharmaceuticals

colonies-blue-2A new H2020 funded project TOPCAPI, involving 8 academic and industry partners from 4 different countries (led by Prof. Takano) will exploit the natural fabrication power of actinomycetes as microbial cell factories to produce high-value pharmaceutical ingredients, in particular the starter compound for the semi-synthesis of a new topical anti-acne drug currently in Phase II clinical trials, and intermediates for the semi-synthetic production of medically important type II polyketide tetracyclines to be used against methicillin-resistant Staphylococcus aureus infections (MRSA). TOPCAPI will focus on the engineering of two bacterial host species: Streptomyces coelicolor and Streptomyces rimosus. These host species will be characterized using systems biology approaches, applying integrated data analysis to transcriptomics and metabolomics experiments, combined with predictive mathematical modelling to drive the rapid improvement of these microbial cell factories for industrial drug production using advanced metabolic and biosynthetic engineering approaches. At the same time, the project will establish an expanded toolbox for the engineering of actinomycete bacteria as production chassis for other high added value compounds.