Mathematical models of experimental microbial evolution
Lead Research Organisation:
University of Exeter
Department Name: Biosciences
Abstract
My research lies at the interface of ecology and evolution and is focused around two key questions in evolutionary ecology: 'What determines species diversity?' and 'How did cooperative behaviour evolve?' These questions are among 25 unsolved problems facing the scientific community over the coming decade highlighted in the 125th anniversary issue of Science. The Science issue also stressed that the advancement of our understanding of the issues relating to the above questions requires a 'major interdisciplinary' effort and this is precisely what my fellowship will address. The fellowship is a collaboration between myself as a mathematical modeller and a group of experimental microbial population biologists namely Dr A Buckling, University of Oxford; Dr T Ferenci, University of Sydney; Professor P Rainey, University of Auckland; and Dr C MacLean, Imperial College London. I will be based at the University of Bath where I will work on the development of mathematical models for a range of projects designed to explore ecological mechanisms involved in the evolution of diversity and cooperation. The studies will be conducted by bringing to bare modern techniques of mathematical analysis and computation on the microbial evolutionary experiments of my collaborators.
People |
ORCID iD |
| Ivana Gudelj (Principal Investigator) |
Publications
Beardmore RE
(2011)
Metabolic trade-offs and the maintenance of the fittest and the flattest.
in Nature
Fuentes-Hernandez A
(2015)
Using a sequential regimen to eliminate bacteria at sublethal antibiotic dosages.
in PLoS biology
Gudelj I
(2016)
Stability of Cross-Feeding Polymorphisms in Microbial Communities.
in PLoS computational biology
Lindsay RJ
(2016)
Harbouring public good mutants within a pathogen population can increase both fitness and virulence.
in eLife
Maharjan R
(2013)
The form of a trade-off determines the response to competition.
in Ecology letters
Meyer JR
(2015)
Biophysical mechanisms that maintain biodiversity through trade-offs.
in Nature communications
Peña-Miller R
(2014)
Testing the optimality properties of a dual antibiotic treatment in a two-locus, two-allele model.
in Journal of the Royal Society, Interface
Rashkov P
(2016)
Kinase Inhibition Leads to Hormesis in a Dual Phosphorylation-Dephosphorylation Cycle.
in PLoS computational biology
| Description | I have developed a range of mathematical models to study the evolution of microorganisms. In particular I have successfully addressed question regarding microbial adaptation to stressful environments. The work has been published in high impact journals including Nature, Plos Biology and Ecology Letters. |
| Exploitation Route | Based on the research developed during this grant, I have now obtained funding from NERC Impact Acceleration Fund to explore possibilities for commercialisation of a bespoke imaging device BioBox. Moreover based on the research developed during this grant, I have also obtained an ERC Consolidator grant starting September 2015 with the long-term goal of: improving rationales for virulence reduction strategies to manage disease; improving rationales for drug deployment in mixed-species communities |
| Sectors | Agriculture, Food and Drink,Education,Healthcare |
| Description | Workshops for school children from disadvantaged background to inspire them to study mathematics at University and apply it to biology, using current outputs from my research. We are also in discussions with an educational charity about developing lesson plans and experiments fitting around the current curriculum to showcase current research as an educational resource for Key stages 3, 4, and 5. The aim is to support the "working scientifically" part of the science curriculum. The end product will be teacher booklets, which will provide structure and legacy for science in the classroom. Collaboration with AstraZeneca to apply my research on Darwinian evolution in microorganisms to cancer. AstraZeneca is funding a postdoc to investigate mechanisms behind hormesis (a significant stimulatory effect of low doses of drugs on cancer cells). |
| First Year Of Impact | 2012 |
| Sector | Education,Healthcare,Pharmaceuticals and Medical Biotechnology |
| Impact Types | Societal |
| Description | Consolidator Grant |
| Amount | € 1,968,392 (EUR) |
| Funding ID | 647292 MathModExp |
| Organisation | European Research Council (ERC) |
| Sector | Public |
| Country | Belgium |
| Start | 09/2015 |
| End | 08/2020 |
| Title | Spatial imaging research tool |
| Description | Over the past 8 years my NERC-funded work (NERC EMS and NERC Advanced Fellowships) has identified a gap in the market in terms of a cost effective device with the ability to produce and analyse real-time, spatially-extended videos of multiple fluorescently-labeled microbial populations grown in co-culture. This would provide a powerful tool for understanding microbial adaptation to abiotic stresses including high temperature, limited resources and antibiotic drugs, both in environmental gradients and within hosts. In the summer of 2013, a physics student was funded through the NERC Research Experience Placement to join our group and together we begun building a prototype of BioBox. This is a bespoke culture device able to take images and videos of fluorescently-labeled mixed microbial communities, interacting in controlled laboratory environments. Subsequently, we obtained NERC IAA funding to conduct market research identifying end users, which has now been competed. |
| Type Of Material | Physiological assessment or outcome measure |
| Provided To Others? | No |
| Impact | Given the specialist nature of the product we conducted the market research by establishing direct contact with schools and research institutions vie e-mail, phone and face-to face meetings, reaching 20 state- and independently-funded schools and over 40 research groups in 3 months. The response has been very positive, with a couple of schools and research groups wishing to purchase the device immediately. |
| Description | Trade-offs and diversity |
| Organisation | University of Sydney |
| Country | Australia |
| Sector | Academic/University |
| PI Contribution | This is an interdisciplinary collaboration looking into the effect of life history trade-offs in the maintenance of diversity in microbial communities. Mathematical models are developed in Gudelj lab (University of Exeter) while the experiential evolution and the development of synthetic communities has been developed in Ferenci lab (University of Sydney). |
| Collaborator Contribution | This is an interdisciplinary collaboration looking into the effect of life history trade-offs in the maintenance of diversity in microbial communities. Mathematical models are developed in Gudelj lab (University of Exeter) while the experiential evolution and the development of synthetic communities has been developed in Ferenci lab (University of Sydney). |
| Impact | This interdisciplinary collaboration involves mathematical modelling, experimental evolution and synthetic biology and has resulted in a number of high impact publications in Ecology Letters. The work has also attracted media attention including articles on the BBC website and Financial Times. |
| Description | BBC news website article |
| Form Of Engagement Activity | A press release, press conference or response to a media enquiry/interview |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Media (as a channel to the public) |
| Results and Impact | BBC news website article: Bacteria give lessons in investment economics, discussing our work published in Maharjan et al Ecology Letters 2013 |
| Year(s) Of Engagement Activity | 2013 |
| Description | BBC radio interview |
| Form Of Engagement Activity | A press release, press conference or response to a media enquiry/interview |
| Part Of Official Scheme? | No |
| Geographic Reach | Regional |
| Primary Audience | Media (as a channel to the public) |
| Results and Impact | BBC Bristol and BBC Wiltshire radio interview: Selfishness can sometimes help the common good, discussing our work published in MacLean et al PloS Biology 2010 |
| Year(s) Of Engagement Activity | 2010 |
| Description | Financial Times article |
| Form Of Engagement Activity | A press release, press conference or response to a media enquiry/interview |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Media (as a channel to the public) |
| Results and Impact | Financial Times Interview: Why Bacteria are model investors, discussing our work published in Maharjan et al Ecology Letters 2013 |
| Year(s) Of Engagement Activity | 2013 |
| Description | Girls into Maths |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | Yes |
| Geographic Reach | Local |
| Primary Audience | Schools |
| Results and Impact | introduced schoolgirls to the area of mathematical biology with the aim of inspiring them to study mathematics at A levels The feedback was overwhelmingly positive and both students and teachers said that they didn't realise that mathematics can be applied to biology |
| Year(s) Of Engagement Activity | 2012 |
| Description | International Conference: Quantitative Evolutionary Dynamics |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | The aim of this workshop is to bridge the gap between mathematical models, laboratory models and natural ecosystems. Speakers talked about plant and human pathogens, natural fungal ecosystems, consortia of symbionts, their responses to antibiotics and viruses and single-cell observations of bacteria in microfluidic devices. |
| Year(s) Of Engagement Activity | 2013 |
| URL | http://www.mmems.org |
| Description | International conference: Coevolution - Models and Microbial Model Systems |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | Coevolution is a fundamental process in evolution. The aim of this workshop is to bring together empiricists using experimental evolution to study coevolution with theoreticians to develop new modelling approaches and to highlight exciting new developments of coevolutionary theory requiring experimental tests. |
| Year(s) Of Engagement Activity | 2010 |
| URL | http://www.mmems.org |
| Description | International conference: Evolution of Antibiotic Resistance |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | The aim of the workshop is to bring together the following three groups of scientists: experts in genotyping, experimental evolution and mathematical modeling. |
| Year(s) Of Engagement Activity | 2009 |
| URL | http://www.mmems.org |
| Description | International conference: Evolution of Microbial Cooperation |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | The workshop will bring together experimentalists and modelers interested in microbial cooperation from molecular and genetic detail thought to population level interactions. |
| Year(s) Of Engagement Activity | 2011 |
| URL | http://www.mmems.org |
| Description | International conference: Evolution of Stress Responses |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | he workshop broadly covered eukaryotic and prokaryotic stress responses at both cell and population levels. |
| Year(s) Of Engagement Activity | 2009 |
| URL | http://www.mmems.org |
| Description | International conference: Mathematics of Microbes: Biological Details of the Evolving Cell |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | An international conference assembling a cross-disciplinary panel of internationally leading speakers presenting current research relating to microbes and antimicrobials, including the action of, and evolution of resistance to antibiotics, phage and peptides. A central theme is 'detail and ecology': how far inside the cell must we look to understand what is happening outside? |
| Year(s) Of Engagement Activity | 2011 |
| URL | http://www.mmems.org |
| Description | Mathematical Biology Summer School |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Schools |
| Results and Impact | This workshop is aimed at schoolchildren from Serbia studying mathematics, physics and computing as an introduction to mathematics applications in biology. The workshop will take place in June 2016 at the University of Exeter. |
| Year(s) Of Engagement Activity | 2016 |
| Description | NEScent working group: Mathematical models, microbes & evolutionary diversification |
| Form Of Engagement Activity | A formal working group, expert panel or dialogue |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | As a part of its 125th anniversary, Science published a special issue containing 125 questions facing the scientific community over the coming decades. Motivation for the proposed working group is based on one of these highlighted problems: What determines species diversity? The working group will bring together mathematicians and life scientists to enhance our understanding of this major question in evolutionary biology. Species diversity can be generated by external factors, such as interactions between organisms, or by internal factors, such as variation in metabolic pathways or complexity within the cell. The proposed working group will use an interdisciplinary approach to studying internally- and externally-generated diversity with the goal of understanding some of the mechanisms that underlie diversification. Our working group emerges from a recent international workshop entitled Mathematical Models and Experimental Microbial Systems: Tools for Studying Evolution at the University of Bath, which brought together experts in mathematics, theoretical evolutionary ecology and microbial experimental evolution. A number of exciting problems have been identified by a core group of scientists from the workshop and thus there is great momentum currently in place to establish a set of new models that will lead to a significant progress towards a general understanding of evolutionary diversification. |
| Year(s) Of Engagement Activity | 2007 |
| Description | New Scientist article |
| Form Of Engagement Activity | A press release, press conference or response to a media enquiry/interview |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Media (as a channel to the public) |
| Results and Impact | New Scientist article: Too much food can be bad for biodiversity, discussing our work published in Forde et al Nature 2008 |
| Year(s) Of Engagement Activity | 2008 |
| Description | Radio Serbia interview |
| Form Of Engagement Activity | A press release, press conference or response to a media enquiry/interview |
| Part Of Official Scheme? | No |
| Geographic Reach | Regional |
| Primary Audience | Media (as a channel to the public) |
| Results and Impact | discussing mathematics for biology in a radio program "A step towards science" |
| Year(s) Of Engagement Activity | 2015 |
| Description | Stoke on Trent sixth form |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Schools |
| Results and Impact | introduced children from disadvantaged background into studying mathematics and biology at university we have established links with the Stoke on Trent sixth form and are planning a series of activities to inspire children from disadvantaged backgrounds to apply to study at university. |
| Year(s) Of Engagement Activity | 2011 |