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. Funded Projects 2023JPIAMRERADIAMR2024-2026£1.2M2023ERCDYNBIOTICS2023-2028£1.8M2023DSTLEfflux-antibiotic therapy2023-2027£92k2023DSTLPhage-antibiotic therapy2023-2027£88k2022BBSRCMulti-layered defences2023-2028£4.7M2022DSTLDrug uptake in Burkholderia2021-2022£25k2021BBSRCSynthetic blastocyst2021-2024£650k2020BBSRCHeterotransport2021-2024£630k2019BBSRCKillerdrop2020-2021£186k2019BBSRCAnti-CRISPR phages2019-2023£642k2019Astra ZenecaAntibiotic bioavailability2019-2023£85k2018MRC/NPL Polypeptide therapeutics2019-2020£97k2018Royal SocietyAntibiotic tolerance markers2018-2019 £20k2018EU COSTINNOGLY2018-2023£500k2017MRC/Dolomite Single-cell gene expression2018-2019£101k2017MRC/DSTLMicrofluidics vs biothreats 2017-2021£92k2017DSTLSingle-pathogen detection2017-2021£84k2017 BBSRC Phytofluidics 2018-2019 £145k2016 GBMF Uncultivated transporters 2017-2021 £715k2016MRC/HummingbSingle-cell antibiodies2016-2017£161k2015Royal SocietyPersister transcriptome2015-2016£15k2015 EU MSCA SINGEK2016-2020 £3.5M 2013LEVERHULMEMembrane transport models2014-2016 £160k Alumni (Name, Position, Next Destination) PostdocsDr Benoit Pons, Postdoctoral research fellow (2019-2024), Postdoctoral research fellow, University of ExeterKrina Chawla, Research Technician (2022-2023)Dr Georgy Glover, Postdoctoral research associate (2022), Epidemiology and information analyst at UKHSADr Jehangir Cama, Postdoctoral research fellow (2019-2022), Co-Founder and Director, ArtioSenseDr Yuewen Zhang, Postdoctoral research associate (2019-2020), Postdoctoral Research Associate, National Physical LaboratoryDr Zehra Kahveci, Postdoctoral research associate (2017-2019), Postdoctoral Research Associate, Spanish National Research CouncilDr Aaron Jeffries, Postdoctoral research fellow (2017), Senior Research Fellow, Biosciences, University of ExeterDr Rosie Bamford, Postdoctoral research associate (2015-2017), Research Technician, Medical School, University of ExeterDr Jeremie Poschmann, Postdoctoral research fellow (2016), Research scientist, University of NantesPhD StudentsAdrian Campey, PhD student (2019-2024), Department of Health and Social Care AdvisorOlivia Goode, PhD student (2018-2022), Postdoctoral research associate, University of ExeterGeorgy Glover, PhD student (2018-2022), Postdoctoral research associate, University of ExeterBrandon Tuck, PhD student (2019-2023), Postdoctoral research fellow, University of NottinghamJake Binsley, PhD student (2019-2023), Product innovation engineer, Osler DiagnosticsErin Attrill, PhD student (2018-2022), Medical Writer, EmotiveRikke Morrish, PhD student (2017-2021), Information Specialist, ProPharma GroupElizabeth Martin, PhD student (2017-2021), Advanced health intelligence analyst, NHSAshley Smith, PhD student (2015-2019), Research Software Engineer, BioSystems Technology LtdFrancesco Valente, PhD student (2016-2020), Senior Research Scientist in Bio-Imaging at Lig-NanowiseTobias Lutz, PhD student (2015-2019), Postdoctoral research associate, Physics, University of ExeterYizhou Tan, PhD student (2014-2018)MbyRes studentsSara Castillo-Vila, MbyRes student (2020-2022), PhD student candidate, University of MallorcaJesmine Ahmed, MbyRes student (2018-2020), Associate microbiologist, GSKAgnieszka Kaczmar, MbyRes student (2017-2019), Research technician, University of ExeterSimona Frustaci, MbyRes Student (2015-2017), PhD student candidate, Physics, University of ExeterUndergraduate students (wet lab projects)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 ExeterLouis 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 ExeterRhiannon Haigh, Summer student (2019), MSc Natural Sciences, University of ExeterFinn 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 CambridgeAlice Carr, Final year MSc Natural Sciences project student (2017-2018), PhD student candidate, Medical School, University of ExeterPaloma 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 ExeterLaura Elliott, Final year BSc Natural Sciences project student (2017), Teacher trainingPaula Usackaite, Final year Bioscience project student and summer placement (2015-2016), Admin and Marketing Executive, Creative Nature SuperfoodsMatt Georgiu, Final year BSc Biosciences project student (2015-2016), Biosciences, University of ExeterAgnieszka Kaczmar, Summer placement student (2015-2016), Open UniversityAshley Smith, Final year BSc Biosciences project student (2015-2016), PhD student candidate, Biosciences, University of ExeterWilliam Ball, Part III project student (Cavendish Laboratory, 2013-2014)Floris Keizer, Part II summer student (Cavendish Laboratory, 2014), PhD Cavendish Laboratory, University of CambridgeEmma Moffatt, Part II summer student (Cavendish Laboratory, 2014), MSc in Biophysics and Molecular Life Sciences, University of BristolVisiting studentsGiulia Tolle, Visiting student (2023), PhD student, University of Cagliari Bing Zhang, Visiting student (2019), PhD student, Institute for Molecular Bioscience, University of QueenslandSophie Vacant, Visiting student (2019), MSc Observatoire Oceanologique de Banyuls sur merRhia Stone, Visiting student (2019), PhD student, Institute for Molecular Bioscience, University of QueenslandMichele Corezzi, Summer student (2017), MSc in Pharmacy, University of CopenhagenYash Bathi, Summer placement student (2016), Master of Technology, Indian Institute of Technology Delhi