Japan Partnering Award: Application of MS-Imaging and Metabolomics in Synthetic Biology Based Strain Improvement of Industrially Important Microbes
Lead Research Organisation:
University of Manchester
Department Name: Chemistry
Abstract
Abstracts are not currently available in GtR for all funded research. This is normally because the abstract was not required at the time of proposal submission, but may be because it included sensitive information such as personal details.
Publications
Biarnes-Carrera M
(2018)
Orthogonal Regulatory Circuits for Escherichia coli Based on the ?-Butyrolactone System of Streptomyces coelicolor
in ACS Synthetic Biology
Breitling R
(2016)
Synthetic Biology of Natural Products.
in Cold Spring Harbor perspectives in biology
Carbonell P
(2016)
Bioinformatics for the synthetic biology of natural products: integrating across the Design-Build-Test cycle.
in Natural product reports
Carbonell P
(2016)
SYNBIOCHEM-a SynBio foundry for the biosynthesis and sustainable production of fine and speciality chemicals.
in Biochemical Society transactions
Del Carratore F
(2019)
Integrated Probabilistic Annotation: A Bayesian-Based Annotation Method for Metabolomic Profiles Integrating Biochemical Connections, Isotope Patterns, and Adduct Relationships.
in Analytical chemistry
Del Carratore F
(2021)
Multi-omics Study of Planobispora rosea, Producer of the Thiopeptide Antibiotic GE2270A.
in mSystems
Del Carratore F
(2022)
Biotechnological application of Streptomyces for the production of clinical drugs and other bioactive molecules
in Current Opinion in Biotechnology
Del Carratore F
(2019)
Computational identification of co-evolving multi-gene modules in microbial biosynthetic gene clusters.
in Communications biology
Jervis A
(2018)
Machine Learning of Designed Translational Control Allows Predictive Pathway Optimization in Escherichia coli
in ACS Synthetic Biology
| Description | The project has enabled collaborations with the Osaka University metabolomics group. We kicked off the program by inviting them to Manchester and holding a Bacterial Metabolomics Workshop on 24th June 2016 with invited speakers: Nicola Zamboni (ETH Zurich), Eiichiro Fukusaki (Osaka University), Karsten Hiller (University of Luxemburg), Sanjay Swarup (National University of Singapore), Shuichi Shimma (Osaka University), Sastia Putri (Osaka University), Rainer Breitling (University of Manchester). A second meeting was organised on 28 June 2019 "Shimadzu Metabolomics Workshop" which was sponsored partly by Shimadzu with speakers from Shimadzu, Osaka University and University of Manchester which also included talks from early career researchers from both Manchester and Shimadzu. There were several coming and going to Osaka University and University of Manchester by 5 individuals to start a close collaboration. During these visits, future grant funding applications were discussed. Visits were conducted to Osaka University Prof. E. Fukusaki, Laboratory of Bio-resource Engineering, Department of Advanced Science and Biotechnology, Graduate School of Engineering: in May 2017 by Katherine Hollywood (SYNBIOCHEM SEO expert in metabolomics); in 2018 with Kamila Schmidt (TA expert in metabolomics) and Eriko Takano; Rainer Breitling and Eriko Takano in 2019; PhD student Nitta Katsuaki visited University of Manchester twice (2017 and 2019) (see below). There was a PhD project conducted through the awarded UK-Japan partnership program: a PhD project with Nitta Katsu (who visited in 2017 and 2019 to Manchester). The project as well as the visit by TA, Kamila Schmidt, developed metabolomics analysis method for Streptomyces (a bacteria which produces the majority of commercial antibiotics) and analysing further to discover antibiotic production yield improvement through metabolomics. In his first visit to Manchester, he mastered the genetic manipulation and growth conditions of Streptomyces and in the second visit extracted RNA from the cultures he has grown in Osaka and to send them for RNAseq analysis in Manchester. His project requires wet experimental work on Streptomyces which can only be done in Takano's lab and thus the two visits were crucial for him to conduct his project. As this shows, this is a true collaborative project, utilising fully the expertise of both groups. His project has now concluded and as a result two joint publications were published. (Nitta K, Breitling R, Takano E, Putri SP, Fukusaki E. Investigation of the effects of actinorhodin biosynthetic gene cluster expression and a rpoB point mutation on the metabolome of Streptomyces coelicolor M1146. J Biosci Bioeng (2021) in press.; Nitta K, Del Carratore F, Breitling R, Takano E*, Putri SP*, Fukusaki E. Multi-omics analysis of the effect of cAMP on actinorhodin production in Streptomyces coelicolor. Front. Bioeng. Biotechnol. (2020) 8, 595552. (*joint corresponding authors)). In spite of the Covid pandemic travel restriction, a new masters student (Mary Faith Adan) joined the collaboration since March 2021, to work on "Metabolome profiling of gamma-butyrolactone (GBL) signaling molecule mutants of Streptomyces coelicolor". This project is aimed to characterise the role of the signaling molecules involved in antibiotic production. Joint monthly meetings were held up to June. However due to illness, Mary Faith was unable to continue her project and she is currently interrupting her studies. She does intend to return to finish her Master Thesis and continue to obtain her PhD. Due to the Covid pandemic and travel restrictions, there was no visits nor secondments possible either in the UK nor in Japan, from March 2020 to present (Feb 2022). Also an international workshop was planned but was cancelled. First phase of Covid travel restrictions were eased and during this period, Takano and Breitling visited University of Osaka, Fukusaki, Shimma, and Putri on 20-21 July 2022 to discuss the planned final Synthetic Biology meeting in November and also for the future possibility for a joint grant funding. The Covid travel restriction to Japan was finally lifted in October 2022. Taking this opportunity, we organised a joint meeting together with our partners in the University of Osaka, Prof Fukusaki, Prof Shimma, and Prof Putri, in Osaka on 18th Nov 2022 entitled " Synthetic Biology approaches and its applications". We invited Japanese and UK speakers to this meeting and made this available remotely so that UK participants can also join. (http://sangyobio-eng.jpn.org/?p=4554) The ke note speakers were Ikuro Abe (University of Tokyo) and Akihiro Kondo (Kobe University) together with Francesco Del Carratore (University of Manchester), Sastia Putri (University of Osaka), Daisuke Kiga (Waseda University), Andy Pitt (University of Manchester), Hiroyasu Onaka (University of Tokyo), Jack Connolly (University of Manchester), Shuichi Shimma (University of Osaka), Erik Hanko (University of Manchester). The meeting was very well attended with over 75 participants, which includes students. Before this meeting, the University of Manchester researchers (Takano, Pitt, Del Carratore, Connolly, Hanko) had one week of discussions with the University of Osaka partners (Fukusaki, Shimma, Putri) and their team which includes MSc, and PhD students (12-20 November 2022). Several ideas for further collaboration were suggested and one to note will be to send strains from Manchester to test the imaging system that University of Osaka, Prof Shimma, has established on the soil bacteria, Streptomyces, to detect any secondary metabolites and signals that can be produced, when growing them next to another microbe. |
| Exploitation Route | Too early to say. |
| Sectors | Agriculture, Food and Drink,Chemicals,Energy,Healthcare,Manufacturing, including Industrial Biotechology,Pharmaceuticals and Medical Biotechnology |
| URL | http://sangyobio-eng.jpn.org/?p=4554 |
| Description | JST |
| Geographic Reach | Asia |
| Policy Influence Type | Participation in a guidance/advisory committee |
| Description | University of Osaka metabolomics |
| Organisation | Osaka University |
| Country | Japan |
| Sector | Academic/University |
| PI Contribution | We aim:To establish strong and successful research collaborations in the analytical area of synthetic biology for fine and speciality chemical between top research groups in the UK and Japan for added potential value to BBSRC and JST science portfolios; Share access to top quality research facilities, technical knowledge and expertise in both institutions, and benefit from the added strengths implied by the complementarity of instrumentation at each institute, helping develop imaging MS as a functional tool in synthetic biology; Provide early career scientists/postdoctoral fellows an opportunity to develop their own expertise and ideas by experiencing international groups and helping prepare their own independent grant applications; Establish joint proof-of-concept research resulting in joint grant applications and collaborative partnerships |
| Collaborator Contribution | The Osaka team will help to establish joint proof-of-concept synthetic biology based research using novel imaging mass spectrometry platforms in tandem with established untargeted metabolomics methodologies;To establish strong and successful research collaborations in the analytical area of synthetic biology for fine and speciality chemical between top research groups in the UK and Japan for added potential value to BBSRC and JST science portfolios; Share access to top quality research facilities, technical knowledge and expertise in both institutions, and benefit from the added strengths implied by the complementarity of instrumentation at each institute, helping develop imaging MS as a functional tool in synthetic biology; Establish joint proof-of-concept research resulting in joint grant applications and collaborative partnerships |
| Impact | The project has just started but we have already started collaborations with the University of Osaka metabolomics group by inviting them to Manchester and holding a Bacterial Metabolomics Workshop on 24th June 2016 with invited speakers: Nicola Zamboni (ETH Zurich), Eiichiro Fukusaki (Osaka University), Karsten Hiller (University of Luxemburg), Sanjay Swarup (National University of Singapore), Shuichi Shimma (Osaka University), Sastia Putri (Osaka University), Rainer Breitling (University of Manchester). In 22-27 May 2017, Katherine Hollywood (named from Manchester) visited Osaka for one week; Eriko Takano and Rainer Breitling visited University of Osaka 14th March 2017 and both gave a seminar to the MSc and PhD students; PhD student Katsuaki Nitta visited to University of Manchester, 26 June-31 July 2017 to learn Streptomyces cultivation techniques and the QExactive analysis; Eriko Takano visited Aug 2017 and had a close discussion with Sastia Putri, Prof Fukusaki and Katsuaki Nitta on the project; Dr Kamila Schmidt (1 Oct - 12 Oct 2018) and Prof Eriko Takano (1- 17 Oct 2018) visited University of Osaka, Prof Fukusaki's lab to work together with Sastia Putri and Katsuaki Nitta on Streptomyces metabolomics using wt M145 strain versus antibiotic overproducer to determine possible metabolic engineering strategies arising from the semi-targetted metabolomics analysis-- this is a multidisciplinary collaboration: synthetic biology, metabolomics, computational modelling; a second workshop was organised on 28 June 2019 "Shimadzu Metabolomics Workshop" which was sponsored partly by Shimadzu with speakers from Shimadzu, Osaka University and University of Manchester which also included talks from early career researchers from both Manchester and Shimadzu; Prof Rainer Breitling and Prof Eriko Takano visited Osaka University on 19-24 July 2019 to give a seminar to the overseas MSc course in Department of Advanced Science and Biotechnology and to discuss further with Prof Fukusaki's group, Sastia Putri's group and Katsuaki Nitta on the use of informatics in the metabolomic analysis; Prof Eriko Takano visited University of Osaka on 25-31 Oct 2019 for futher discussions; Prof Eriko Takano visited University of Osaka on 15 -28 Feb 2020 to participate in the final year MSc presentations of the MSc course in Department of Advanced Science and Biotechnology and to discuss with Katsuaki Nitta on his PhD project. This was a crucial meeting as Katsuaki Nitta will need to finish his thesis by Dec 2020 and detailed discussion took place for publication strategy. Takano, Breitling lab in University of Manchester had several Skype conferences with Fukusaki lab, Sastia Putri and Katsuaki Nitta on metabolic modelling of Streptomyces coelicolor -- this is a multidisciplinary collaboration on metabolomics, computational modelling; Takano has been invited to be a honorary Professor/Cross-appointment at the University of Osaka, allowing her to stay in Osaka for 4 weeks/year from April 2018-March 2020 A new project collaboration has started with a MSc student Marvin Nathanael Iman, who is in the Fukusaki lab, however the student has decided to move on and has now started a new project. Takano had several zoom meetings with Sastia Putri and Katsuaki Nitta on Nitta's PhD project. Nitta's PhD project has led to two publications: Nitta K, Breitling R, Takano E, Putri SP, Fukusaki E. Investigation of the effects of actinorhodin biosynthetic gene cluster expression and a rpoB point mutation on the metabolome of Streptomyces coelicolor M1146. J Biosci Bioeng (2021) in press.; Nitta K, Del Carratore F, Breitling R, Takano E*, Putri SP*, Fukusaki E. Multi-omics analysis of the effect of cAMP on actinorhodin production in Streptomyces coelicolor. Front. Bioeng. Biotechnol. (2020) 8, 595552. (*joint corresponding authors). A new MSc student Mary Faith Adan has started in University of Osaka to collaboration on metabolomics on Streptomyces supervised by Dr Sastia Putri and Prof Fukusaki in Feb 2021. |
| Start Year | 2016 |
| Description | 2021 iGEM Manchester team supervisor |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Undergraduate students |
| Results and Impact | More than 300 UG and more than 100 researcher attended the iGEM jamboree where we presented our project to bring awareness and discussions in synthetic biology. |
| Year(s) Of Engagement Activity | 2021 |
| URL | https://2021.igem.org/Team:Manchester |
| Description | 2022 iGEM Manchester team supervisor |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Undergraduate students |
| Results and Impact | More than 300 UG and more than 100 researcher attended the iGEM jamboree where we presented our project to bring awareness and discussions in synthetic biology. |
| Year(s) Of Engagement Activity | 2022 |
| URL | https://2022.igem.wiki/manchester/ |
| Description | iGEM 2020 |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Undergraduate students |
| Results and Impact | Organised the Manchester iGEM team for 2020. iGEM is an annual international student competition in synthetic biology, providing a great interdisciplinary learning opportunity for our students from all faculties. This year's Manchester iGEM team worked throughout the summer in very unusual circumstances. The team project was Hipposol, aimed at producing an eco-friendly sunscreen, derived from hippopotamus sweat, in genetically engineered bacteria. They were probably the first iGEM team to successfully use computational retrosynthesis for their project, and with the help of the Manchester Business School they comprehensively explored the social and economic implications of their ideas using a Responsible Research and Innovation approach. The Manchester 2020 iGEM team won a Gold medal and was nominated for the "Best Supporting Entrepreneurship" award in this year's iGEM (Virtual) Giant Jamboree |
| Year(s) Of Engagement Activity | 2020 |
| URL | https://2020.igem.org/Team:Manchester |
| Description | iGEM participation |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Undergraduate students |
| Results and Impact | Takano has organised the Manchester iGEM team since 2012 with Prof Rainer Breitling. The iGEM competition (International Genetically Engineered Machine competition: https://igem.org/Main_Page) is a prestigious international synthetic biology event, with more than 300 participating teams from international universities (form all over the world), who present their summer research at a Giant Jamboree in Boston. iGEM is a major opportunity for undergraduate students to acquire interdisciplinary and transferable skills and to show their achievements in an international setting. The total number of participants is well over 500 with each team having more that 10 members. Our Manchester teams have been very successful and have achieved a gold medal for four years; in 2016 they won not only the gold medal, but also scooped the special award for 'Best Computational Model' - and were also shortlisted for the 'Best Education and Public Engagement' award. We had very interesting topics from Palm oil production in E. coli to alcohol patch on skin to detect and make aware alcohol consumption. Many discussions involving NGOs(e.g. friends of the earth, green peace, alcohol anonymous) and public institutions (e.g. police, NHS hospitals, FBI) and industry (cheese makers, brewery, confectionery). All of the teams achievements have increased awareness in synthetic biology and sparked many discussion afterwards. We still receive interest for a topic which was done in 2012. More information of the Manchester teams can be found at http://2018.igem.org/Team:Manchester http://2017.igem.org/Team:Manchester http://2016.igem.org/Team:Manchester; http://2015.igem.org/Team:Manchester-Graz; http://2013.igem.org/Team:Manchester |
| Year(s) Of Engagement Activity | 2013,2014,2015,2016,2017,2018 |
| URL | http://2018.igem.org/Team:Manchester |