Pagliara Group
Membrane Transport in Antimicrobial Resistance
Our research focuses on understanding the membrane transport mechanisms underpinning phenotypic diversification without genetic variations within cellular populations. A major area of research within the group is the study of antimicrobial resistance which constitutes one of the greatest challenges for modern society. We use a variety of cutting-edge approaches including microfluidics-based microscopy, next generation sequencing and microbiology assays to investigate membrane transport and response to antibiotics in bacterial populations and in individual bacteria. Moreover, we also use these cutting-edge approaches to investigate research questions in a broader context including host-pathogen interactions, membrane transport at the origin of life and cellular ageing
Aims
1. To determine the environmental factors and the molecular mechanisms underlying heterogeneity in molecular uptake in unicellular organisms such as bacteria, fungi and mammalian cells.
2. To elucidate the mechanisms underlying survival to antimicrobials of subsets within clonal microbial populations.
3. To understand the dynamics of inter-species interactions at the scale of the individual cell, particularly between the host and its pathogen as well as between symbionts.
4. To investigate how ageing shapes the composition of clonal microbial populations.
5. To understand how membrane transport at the origin of life shaped the evolution of molecular machineries.
Research Areas
Single-Cell Biology
We have recently begun to understand that there are important differences between cells which have the same genetic make-up. Therefore, we need to study the behaviour of thousands individual cells within a population, this requiring the development of single-cell technologies including novel microfluidic and imaging tools. Our research group uses these tools to understanding how individual cells within a population specialise to perform specific functions with an emphasis on their capabilities to exchange molecules with their environment and with other cells.
Antibiotic Accumulation and Efficacy
Antibiotics play a fundamental role in modern medicine, but drug-resistant pathogens now exist for all known antibiotics. In combination with a major void in antibiotic discovery, this has led to predictions that bacterial infections will cause 10 million premature deaths annually by 2050. Our research tackle this crucial societal issue by quantifying both the uptake of existing and novel drugs in individual bacterial pathogen as well as the efficacy of such drugs in completely clearing out a bacterial infection.
Host-Pathogen Interactions
Individual cells interact with their neighbours in a variety of different ways both beneficial and detrimental for the wellbeing. Our research focuses on the study of the relationship between bacteria and their bacteriophage which is relevant for next generation phage-antibiotic therapy to counter the current antimicrobial resistance crisis.
Membrane Transport at the Origin of Life
Molecular exchange across cellular membranes is at the basis of life. Our research sheds new light on the heterogeneity of molecular uptake within extant cellular populations and within model cellular membranes that recapitulate archaeal and bacterial membranes during the early stages of the evolution of cellular compartments at the so-called lipid divide.
Ageing
Ageing is the decline in reproductive success and survival with advancing age and has been well documented across a diverse range of multicellular organisms where it is thought to arise from the progressive accumulation of defects. Our research investigates the mechanisms underlying the natural course of ageing in unicellular organisms, such as bacteria, in the absence of external stressors.
Group Members
Principal Investigator
Prof Stefano Pagliara, s.pagliara@exeter.ac.uk. Stefano’s research programme is focused on molecular transport across biological membranes with the goal of understanding how transport links with single cell responses to changes in the environment and the emergence of antimicrobial resistance in bacterial populations.
Research Fellows
Dr Urszula Lapinska, U.Lapinska@exeter.ac.uk. Ula is investigating the mechanisms underlying antibiotic accumulation in polymicrobial communities as part of the ERC Consolidator project DYNBIOTICS, in collaboration with Prof Mark Blaskovich at the University of Queensland and Prof Krasi Tsaneva-Atanasova.
Dr Maureen Micaletto, M.Micaletto@exeter.ac.uk. Maureen is investigating the mechanisms underlying the interactions between phage and antibiotics in Pseudomonas aeruginosa as part of the BBSRC sLoLa MultiDefence project.
Dr Ilayda Sultan Donmez Eryilmaz, S.Donmez-Eryilmaz@exeter.ac.uk. Ily is developing new technologies to interrogate bacterial responses to antibiotics at the level of the individual bacterium as part of the ERC Consolidator project DYNBIOTICS.
Dr Sophia Zborowsky, S.Zborowsky@exeter.ac.uk. Sophia is investigating the regulatory networks underpinning antibiotic accumulation as part of the ERC Consolidator project DYNBIOTICS.
Dr Tailise Rodrigues, T.de-Souza-Guerreiro-Rodrigues@exeter.ac.uk. Tailise is developing new approaches for Effective RApid DIagnostics and treatment of AntiMicrobial Resistant bacteria as part of the ERADIAMR JPIAMR Consourtium.
PhD Students
Ka Kiu Lee, kkl204@exeter.ac.uk. Ka Kiu is investigating the transcriptional and translational mechanisms underlying antibiotic accumulation, in collaboration with Prof Mark Blaskovich at the University of Queensland, Prof Krasi Tsaneva-Atanasova and Dr Ben Housden.
Megan Fletcher, mf616@exeter.ac.uk. Megan is studying novel antibiotic-phage combinations for treating bacterial infections such as meliodosis, in collaboration with Prof Sarah Harding at Dstl and Prof Sunee Korbsrisate at the University of Mahidol.
Samuel Krauss, sk759@exeter.ac.uk. Samuel is investigating phage-bacteria interactions at the single-cell level in collaboration with Prof Mark Blaskovich and Dr Patrick Harris at the University of Queensland.
Gayathri Chandran, gc576@exeter.ac.uk. Gayathri is investigating the impact of inter-kingdom interacations on the efficacy of antibiotics and antifungals against polymicrobial communities in collaboration with Prof Adilia Warris.
Marina Filippidou, mt871@exeter.ac.uk. Marina is developing a machine learning pipeline for automated analysis and modelling of single-responses from microfluidics-based time-lapse microscopy in collaboration with Dr Margaritis Voliotis and Dr Sareh Rowlands.
Will Miller, wm376@exeter.ac.uk.Will is developing a microfluidics-based platform for antibiotic discovery in collaboration with Prof Sarah Harding at Dstl, Prof Paul Race at the University of Newcastle and Dr Fabrizio Pertusati at the University of Cardiff.
Funded Projects
| 2024 | Moore Foundation | Stereochemistry of Life | 2025-2028 | £1.5M |
| 2023 | JPIAMR | ERADIAMR | 2024-2026 | £1.2M |
| 2023 | ERC | DYNBIOTICS | 2023-2028 | £1.7M |
| 2023 | DSTL | Efflux-antibiotic therapy | 2023-2027 | £92k |
| 2023 | DSTL | Phage-antibiotic therapy | 2023-2027 | £88k |
| 2022 | BBSRC | Multi-layered defences | 2023-2028 | £4.7M |
| 2022 | DSTL | Drug uptake in Burkholderia | 2021-2022 | £25k |
| 2021 | BBSRC | Synthetic blastocyst | 2021-2024 | £650k |
| 2020 | BBSRC | Heterotransport | 2021-2024 | £630k |
| 2019 | BBSRC | Killerdrop | 2020-2021 | £186k |
| 2019 | BBSRC | Anti-CRISPR phages | 2019-2023 | £642k |
| 2019 | Astra Zeneca | Antibiotic bioavailability | 2019-2023 | £85k |
| 2018 | MRC/NPL | Polypeptide therapeutics | 2019-2020 | £97k |
| 2018 | Royal Society | Antibiotic tolerance markers | 2018-2019 | £20k |
| 2018 | EU COST | INNOGLY | 2018-2023 | £500k |
| 2017 | MRC/Dolomite | Single-cell gene expression | 2018-2019 | £101k |
| 2017 | MRC/DSTL | Microfluidics vs biothreats | 2017-2021 | £92k |
| 2017 | DSTL | Single-pathogen detection | 2017-2021 | £84k |
| 2017 | BBSRC | Phytofluidics | 2018-2019 | £145k |
| 2016 | Moore Foundation | Uncultivated transporters | 2017-2021 | £715k |
| 2016 | MRC/Hummingb | Single-cell antibiodies | 2016-2017 | £161k |
| 2015 | Royal Society | Persister transcriptome | 2015-2016 | £15k |
| 2015 | EU MSCA | SINGEK | 2016-2020 | £3.5M |
| 2013 | LEVERHULME | Membrane transport models | 2014-2016 | £160k |
Alumni (Name, Position, Next Destination)
Postdocs
Dr Benoit Pons, Postdoctoral research fellow (2019-2024), Maitre de Conference, University of Toulouse
Krina Chawla, Research Technician (2022-2023)
Dr Georgy Glover, Postdoctoral research associate (2022), Epidemiology and information analyst at UKHSA
Dr Jehangir Cama, Postdoctoral research fellow (2019-2022), Co-Founder and Director, ArtioSense
Dr Yuewen Zhang, Postdoctoral research associate (2019-2020), Postdoctoral Research Associate, National Physical Laboratory
Dr Zehra Kahveci, Postdoctoral research associate (2017-2019), Postdoctoral Research Associate, Spanish National Research Council
Dr Aaron Jeffries, Postdoctoral research fellow (2017), Senior Research Fellow, Biosciences, University of Exeter
Dr Rosie Bamford, Postdoctoral research associate (2015-2017), Research Technician, Medical School, University of Exeter
Dr Jeremie Poschmann, Postdoctoral research fellow (2016), Research scientist, University of Nantes
PhD Students
Adrian Campey, PhD student (2019-2024), Department of Health and Social Care Advisor
Olivia Goode, PhD student (2018-2022), Postdoctoral research associate, University of Exeter
Georgy Glover, PhD student (2018-2022), Postdoctoral research associate, University of Exeter
Brandon Tuck, PhD student (2019-2023), Postdoctoral research fellow, University of Nottingham
Jake Binsley, PhD student (2019-2023), Product innovation engineer, Osler Diagnostics
Erin Attrill, PhD student (2018-2022), Medical Writer, Emotive
Rikke Morrish, PhD student (2017-2021), Information Specialist, ProPharma Group
Elizabeth Martin, PhD student (2017-2021), Advanced health intelligence analyst, NHS
Ashley Smith, PhD student (2015-2019), Research Software Engineer, BioSystems Technology Ltd
Francesco Valente, PhD student (2016-2020), Senior Research Scientist in Bio-Imaging at Lig-Nanowise
Tobias Lutz, PhD student (2015-2019), Postdoctoral research associate, Physics, University of Exeter
Yizhou Tan, PhD student (2014-2018)
MbyRes students
Sara Castillo-Vila, MbyRes student (2020-2022), PhD student candidate, University of Mallorca
Jesmine Ahmed, MbyRes student (2018-2020), Associate microbiologist, GSK
Agnieszka Kaczmar, MbyRes student (2017-2019), Research technician, University of Exeter
Simona Frustaci, MbyRes Student (2015-2017), PhD student candidate, Physics, University of Exeter
Undergraduate students (wet lab projects)
Georgia Thomson, Final year BSc Biosciences project student (2024-2025) Aimee Usher, Final year BSc Biosciences project student (2024-2025) Emilie Calloud, , Final year BSc Biosciences project student (2023-2024) Caroline Winkel, Final year BSc Biosciences project student (2022-2023) Freya Williamson, Final year MSc Biosciences project student (2021-2022)
Charlotte Harvey, Final year BSc Natural Sciences project student (2021-2022)
Justine Locmele, Final year BSc Natural Sciences project student (2021-2022)
Filipe Maia, Final year BSc Natural Sciences project student (2021-2022)
Ellen Rogers, Final year BSc Biosciences project student (2021-2022)
Aaron Walker, Final year MSc Natural Sciences project student (2019-2020)
Jesmine Tomlinson, Final year MSc Biosciences project student (2020-2021)
Ka Kiu Lee, Final year BSc Biosciences project student (2019-2020), PhD student candidate, Biosciences, University of Exeter
Louis Clement-Harris, Final year MSc Natural Sciences project student (2019-2020)
Natalie Cotterell, MSc Natural Sciences project student (2019-2020)
James Cridland, Summer student (2019), MSc Natural Sciences, University of Exeter
Rhiannon Haigh, Summer student (2019), MSc Natural Sciences, University of Exeter
Finn Merlett, Final year MSc Natural Sciences project student (2018-2019)
Thomas Ledgerwood, Final year MSc Natural Sciences project student (2018-2019)
Emma Baker, Final year BSc Natural Sciences project student (2019)
Samuel Wallace, Final year BSc Biosciences project student (2018-2019)
Hanro Rossouw, Final year BSc Biosciences project student (2018-2019)
Katherine Webber, Final year BSc Biosciences project student (2017-2018), PhD student candidate, Physics, University of Cambridge
Alice Carr, Final year MSc Natural Sciences project student (2017-2018), PhD student candidate, Medical School, University of Exeter
Paloma Marsolo, Final year BSc Biosciences project student (2017-2018)
Chris Smith, Final year BSc Biosciences project student (2016-2017)
Georgy Glover, Final year BSc Biosciences project student (2016-2017), PhD student candidate, Physics, University of Exeter
Laura Elliott, Final year BSc Natural Sciences project student (2017), Teacher training
Paula Usackaite, Final year Bioscience project student and summer placement (2015-2016), Admin and Marketing Executive, Creative Nature Superfoods
Matt Georgiu, Final year BSc Biosciences project student (2015-2016), Biosciences, University of Exeter
Agnieszka Kaczmar, Summer placement student (2015-2016), Open University
Ashley Smith, Final year BSc Biosciences project student (2015-2016), PhD student candidate, Biosciences, University of Exeter
William Ball, Part III project student (Cavendish Laboratory, 2013-2014)
Floris Keizer, Part II summer student (Cavendish Laboratory, 2014), PhD Cavendish Laboratory, University of Cambridge
Emma Moffatt, Part II summer student (Cavendish Laboratory, 2014), MSc in Biophysics and Molecular Life Sciences, University of Bristol
Visiting students
Giulia Tolle, Visiting student (2023), PhD student, University of Cagliari Bing Zhang, Visiting student (2019), PhD student, Institute for Molecular Bioscience, University of Queensland
Sophie Vacant, Visiting student (2019), MSc Observatoire Oceanologique de Banyuls sur mer
Rhia Stone, Visiting student (2019), PhD student, Institute for Molecular Bioscience, University of Queensland
Michele Corezzi, Summer student (2017), MSc in Pharmacy, University of Copenhagen
Yash Bathi, Summer placement student (2016), Master of Technology, Indian Institute of Technology Delhi
