Professor Tim Mitchell BSc, PhD, FRCPath

Professor Tim Mitchell

Institute of Microbiology and Infection
Emeritus Professor of Microbial Infection and Immunity
Joint Microbiology Theme Lead SRMRC

Contact details

Address
Biosciences Building
Institute of Microbiology and Infection
College of Medical and Dental Sciences
University of Birmingham
Edgbaston
Birmingham
B15 2TT
UK

Tim Mitchell is Emeritus Professor of Microbial Infection and Immunity in the Institute of Microbiology and Infection.

Tim has published over 200 research papers in scientific journals as well as reviews and book chapters in the fields of microbial pathogenesis and immunity. He has received major grants from Wellcome Trust, European Union, Medical Research Council and PATH. He has good links with industry for translational research.

Tim Mitchell is a leading member of the NIHR SRMRC. You can find out more about the work of this research centre on the SRMRC website.

Qualifications

  • Fellow of Royal College of Pathologists 2004
  • PhD Microbiology 1986
  • BSc (Hons) Biological Sciences 1983

Biography

Tim Mitchell completed his PhD at the University of Birmingham studying the role of enterotoxin A in the pathogenesis of infections caused by Clostridium difficile. He was then awarded a Wellcome Trust travelling fellowship to study the role of cGMP-dependent protein kinases in the mechanism of action of bacterial toxins at Erasmus University in Rotterdam, The Netherlands. Tim returned from the Netherlands to a postdoctoral position in the laboratory of Graham Boulnois at the University of Leicester where he started working with pneumolysin, the pore-forming toxin produced by Streptococcus pneumoniae. On the basis of this work he was awarded a Royal Society University Research Fellowship that allowed him to establish an independent research group at the University of Leicester. The work done during this period defined some of the mechanisms of pore formation by the pneumococcal toxin and its role in the pathogenesis of pneumococcal infection. This led to the development of toxoids that were evaluated as vaccine candidates. In 1996 Tim was appointed to the Chair of Microbiology at the University of Glasgow where he continued work on the pathogenesis of pneumococcal infection and developed approaches to exploit bacterial genomics in these studies. In 2012 he moved to his current position as Professor of Microbial Infection and Immunity at the University of Birmingham.

Teaching

Research

Major research interests concern the investigation of the pathogenesis of bacterial infectious diseases. The molecular study of these processes can be used to design or modify vaccines and improve therapeutic approaches.

The interaction of pathogens with the host is a complex one. Pathogens produce numerous factors that interact with the host during pathogenesis, including capsules, enzymes and toxins. Tim is interested in investigating this interaction by genetic manipulation of the pathogen and the host (via transgenic technology). Recent work has been concerned with disease caused by Streptococcus pneumoniae. Tim has been involved in the study of a number of virulence factors from this organism, including the protein toxin pneumolysin. A detailed structure function study of this protein allowed the identification of several important functional regions of the toxin. Modification of these regions led to the development of a toxoided protein that is now being evaluated as an addition to the human vaccine.

With the availability of the genome sequences of many bacterial pathogens, it is now possible to investigate the pathogenesis of several bacterial infections at the molecular level. Analysis of bacterial genome sequences allows the identification of the basis of important differences between strains that are responsible for altered ability to cause disease. A combination of the use of bacterial mutants, animal models and transgenic animal models allows us to probe the host/pathogen interaction. We can then use this information to assist in the design of new vaccines or therapies.

Other activities

  • Undergraduate external examiner in microbiology:
    • University of Aberdeen 1998-2001
    • University of Bristol 1998-2002
  • External examiner for the Masters degree in Medical Microbiology at University of Aberdeen 2009–2013
  • Examiner for the Masters Degree in Microbiology and Immunology at University of Nottingham 2010-2014
  • External examiner for 33 PhD examinations
  • Danish Research Council Panel Member 2011-2014
  • Research Council of Norway - Grant Panel Member 2012-2015
  • Meningitis UK Grant panel
  • Scottish Healthcare Associated Infection Prevention Institute (SHAIPI) - Independent Chair of Management Group

Publications

Nerlich A, von Wunsch Teruel I, Mieth M, Hönzke K, Rückert JC, Mitchell TJ, Suttorp N, Hippenstiel S, Hocke AC. Reversion of Pneumolysin-Induced Executioner Caspase Activation Redirects Cells to Survival. J Infect Dis. 2021 Jun 4;223(11):1973-1983.

Letsiou E, Teixeira Alves LG, Fatykhova D, Felten M, Mitchell TJ, Müller-Redetzky HC, Hocke AC, Witzenrath M. Microvesicles released from pneumolysin-stimulated lung epithelial cells carry mitochondrial cargo and suppress neutrophil oxidative burst. Sci Rep. 2021 May 5;11(1):9529. 

Badgujar DC, Anil A, Green AE, Surve MV, Madhavan S, Beckett A, Prior IA, Godsora BK, Patil SB, More PK, Sarkar SG, Mitchell A, Banerjee R, Phale PS, Mitchell TJ, Neill DR, Bhaumik P, Banerjee A. Structural insights into loss of function of a pore forming toxin and its role in pneumococcal adaptation to an intracellular lifestyle. PLoS Pathog. 2020 Nov;16(11):e1009016. 

Panagiotou S, Chaguza C, Yahya R, Audshasai T, Baltazar M, Ressel L, Khandaker S, Alsahag M, Mitchell TJ, Prudhomme M, Kadioglu A, Yang M. Hypervirulent pneumococcal serotype 1 harbours two pneumolysin variants with differential haemolytic activity. Sci Rep. 2020 Oct 14;10(1):17313. 

Watson K, Russell CD, Baillie JK, Dhaliwal K, Fitzgerald JR, Mitchell TJ, Simpson AJ, Renshaw SA, Dockrell DH. Developing Novel Host-Based Therapies Targeting Microbicidal Responses in Macrophages and Neutrophils to Combat Bacterial Antimicrobial Resistance. Front Immunol. 2020;11:786. doi: 10.3389/fimmu.2020.00786. eCollection 2020. Review. 

Preston JA, Bewley MA, Marriott HM, McGarry Houghton A, Mohasin M, Jubrail J, Morris L, Stephenson YL, Cross S, Greaves DR, Craig RW, van Rooijen N, Bingle CD, Read RC, Mitchell TJ, Whyte MKB, Shapiro SD, Dockrell DH. Alveolar Macrophage Apoptosis-associated Bacterial Killing Helps Prevent Murine Pneumonia. Am J Respir Crit Care Med. 2019 Jul 1;200(1):84-97. 

Hupp S, Grandgirard D, Mitchell TJ, Leib SL, Hathaway LJ, Iliev AI. Pneumolysin and the bacterial capsule of Streptococcus pneumoniae cooperatively inhibit taxis and motility of microglia. J Neuroinflammation. 2019 May 18;16(1):105.

Maurer J, Hupp S, Pillich H, Mitchell TJ, Chakraborty T, Iliev AI. Missing elimination via membrane vesicle shedding contributes to the diminished calcium sensitivity of listeriolysin O. Sci Rep. 2018 Oct 26;8(1):15846. 

Köffel R, Wolfmeier H, Larpin Y, Besançon H, Schoenauer R, Babiychuk VS, Drücker P, Pabst T, Mitchell TJ, Babiychuk EB, Draeger A. Host-Derived Microvesicles Carrying Bacterial Pore-Forming Toxins Deliver Signals to Macrophages: A Novel Mechanism of Shaping Immune Responses. Front Immunol. 2018;9:1688. 

Gutbier B, Neuhauß AK, Reppe K, Ehrler C, Santel A, Kaufmann J, Scholz M, Weissmann N, Morawietz L, Mitchell TJ, Aliberti S, Hippenstiel S, Suttorp N, Witzenrath M. Prognostic and Pathogenic Role of Angiopoietin-1 and -2 in Pneumonia. Am J Respir Crit Care Med. 2018 Jul 15;198(2):220-231. 

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