Staff Profile
Dr Anjam Khan
Principal Investigator and Director Infectious Diseases Facility
- Telephone: +44 (0) 191 208 7066
- Personal Website: https://www.ncl.ac.uk/medical-sciences/research/institutes/biosciences/
- Address: Biosciences Institute (NUBI)
Cookson Building
Faculty of Medical Sciences
Newcastle University
Framlington Place
Newcastle
NE2 4HH
UK
Background
Roles and Responsibilities
Biosciences Institute (NUBI):
Chair, Microbiological Hazards and Genetic Modification Committee
Member, Executive Board
Member, Safety Committee
Academic Lead for Equality, Diversity, and Inclusion (EDI)
Chair, EDI Steering Committee
Faculty of Medical Sciences (FMS):
Director, Infectious Diseases Facility (IDF)
Academic Promotions Committee (Elected Term 2022-2025)
Member, Faculty EDI Committee (FEDIC)
Member, Equality Project (incl Athena Swan):[1] Self-Assesment Team; [2] WS1-Qualitative Data
Vice-Chair, Infectious Diseases Facility (IDF) Management-PI User Group
University (NU):
Senator (Elected Term: 2021-2024)
Honorary Degree's Committee
University Biosafety Committee
Race Equality Network (NU-REN) Steering Committee
Race Equality Charter (REC) Team: Research Workstream
Senate Representative, University EDI Committee
External Roles and Responsibilities
Microbiology Society: Members Panel
Microbiology Society: Sustainability (Leadership & Finance) Committee
Qualifications
PhD in Molecular Biology, with Professor John Scaife FRSE, University of Edinburgh
BSc Hons in Biochemistry, University of Manchester, Institute of Science and Technology
Previous Positions
University of Cambridge, Postdoctoral Research Associate
University of Newcastle, Lecturer in Microbiology
Research
I am a member of the Newcastle University Biosciences Institute (NUBI) and my research contributes to the Research Themes:
- Microbes in Health and Disease
- Molecular and Cellular Microbiology
- Immunity and Inflammation
Research Interests
Our major research objectives are to understand the biology of Salmonella and gain insights into the mechanisms by which it causes disease. We are using a multi-disciplinary approach with an international team of collaborators to fulfil these objectives. The group has a broad portfolio of research within the following themes as outlined below, and further details of the research are available upon request.
Quorum Sensing and Host-Pathogen Cross-Talk
Research on quorum sensing has provided vivid insights into the mechanisms by which bacteria coordinate their efforts and behave in a “multicellular” fashion. We are investigating how Salmonella use small signal molecules called autoinducers to communicate with each other, and aim at identifying the genes and physiological processes regulated by quorum sensing. Strikingly, we have revealed inter-kingdom crosstalk between pathogens and their hosts. Thus enabling Salmonella to “eavesdrop” on host communication systems by sensing neuroendocrine stress hormones and using these signals as cues to regulate the expression of genes important in virulence. These neuroendocrine stress hormones such as noradrenaline (norepinephrine) are present at biologically relevant concentrations in the gastrointestinal tract and are used as environmental cues by the pathogen to regulate virulence gene expression. This research is a close multidisciplinary collaboration with Paul Williams, Nottingham University; Mark Jepson, Bristol University.
Understanding the Mechanistic Basis of Competitive Interactions between Salmonella and the Intestinal Microbiota
Bacterial infections are a major cause of morbidity and mortality in humans. The emergence of antimicrobial resistance has exacerbated the impact of these infections making them harder to treat and increasing mortality. Recent advances have revealed the major roles the intestinal microbiome play in health and disease within hosts. Following ingestion, the foodborne pathogen Salmonella faces fierce competition from the resident intestinal microbiota. However, Salmonella species have developed strategies enabling them to outcompete the intestinal microbiota and undergo a rapid growth-burst resulting in disease. We have developed gastrointestinal tract-relevant, in vitro co-culture conditions, and our objectives are to characterise Salmonella-microbiota interactions, identifying the molecular mechanisms mediating growth-bursts and pathogenesis. This research is a close multidisciplinary collaboration with: David Bolam, Newcastle University; Jay Hinton and Heather Allison, Liverpool University, Lindsay Hall, Quadram Institute, Norwich.
Exploiting Synthetic Biology to Engineer Vaccines Against Emerging Pathogens Using Novel Bacterial-Based Delivery Platforms
Emerging pathogens represent a major threat to global health. In the last 20 years we have seen the emergence of the corona virus SARS-CoV-1 in 2003, Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012, and very recently Ebola and Zika viruses. Never before in modern times have we seen such a rapid and devastating global pandemic as COVID-19. Severe Acute Respiratory Syndrome Coronavirus-2, SARS-CoV-2, is responsible for the disease COVID-19. This pandemic will remain until an effective vaccine which protects against disease is developed. This is not a straight-forward process and we still do not have effective vaccines against malaria, TB, or HIV in spite of huge international efforts over many years. We are contributing to the development of novel bacterial vaccine platforms against existing bacterial (Shigella-ETEC) and emerging viral pathogens (Ebola virus, Zika virus, and SARS-CoV-2). Salmonella can be genetically manipulated to increase the shedding of outer membrane vesicles (OMVs). Further mutations can be introduced into genes encoding key enzymes to reduce the reactogenicity of OMVs, by modifying lipid A structure. These outer membrane vesicles are naturally immunogenic, and by expressing recombinant antigens from other pathogens within them as cargo, e.g. SARS-CoV-2, they can be exploited to generate vaccines to protect against the novel corona virus. As these vesicles are potently immunogenic and cost-effective to produce, they have great potential as a novel vaccine delivery platform, much needed for our readiness in rapidly dealing with new emerging pathogens. This research is a close multidisciplinary collaboration with: Pietro Mastroeni, Cambridge University; Gary Gobinger, Universite Laval, Canada; Alain Kohl, Glasgow University; Francesca Micolli, GlaxoSmithKline Vaccines; Robin Shattock, Imperial College London.
Microbial Biofilms and Infection
Implants are an indispensable part of orthopaedics and their use has revolutionised the treatment of patients with fractures and with debilitating diseases like osteoarthritis. The introduction of an implant inside the body is always associated with the risk of microbial infection, as they are foreign bodies inside their hosts and act as a focal point of infection. The human immune system can deal with systemic infection but these implants provide a refuge for bacteria where immune system and systemic antibiotics have a diminished effect. Bacteria often produce multicellular assemblies known as biofilms sometimes referred to as a “city of microbes”. This community of cells are shielded in a self-produced protective extracellular matrix composed of polysaccharides, proteins and eDNA. Biofilm formation represents a highly evolved prokaryotic defence mechanism play an important role in implant associated infections leading to chronic infections untreatable by antibiotics. We have identified novel biofilm dispersing agents and are testing their efficacy against biofilm formation by clinically relevant bacterial species, and investigating their use in the clinical management of posterior joint infections (PJI). This research is a close multidisciplinary collaboration with Grant Burgess, SNES Newcastle University, and Mike Reed Consultant Trauma and Orthopaedic Surgeon for Northumbria Healthcare NHS Foundation Trust.
The Research Group
Postdoctoral Research Associate
Bethany Gollan (MRC CiC)
Postgraduate PhD Students:
John “Jack” Clark-Corrigall (BBSRC DTP3 PhD Studentship)
Bayan Qadri (Royal Saudi Arabian Government PhD Studentship)
Alaa Alshuwaier (Royal Saudi Arabian Government PhD Studentship)
Postdoctoral Research Associate - Joint:
Dr Yuming Cai (funded by Heraeus Medical GmbH)
Co-supervised with Prof Grant Burgess in School of Natural and Environmental Sciences, and Prof Mike Reed, Consultant Trauma and Orthopaedic Surgeon for Northumbria Healthcare NHS Foundation Trust.
Faculty Research Fellow:
Hosting and mentoring faculty research fellow James Connolly
MD Students:
Dr Puneet Tailor, Orthopaedic Surgeon (Co-supervised with Prof Grant Burgess and Prof Mike Reed)
Dr Prateek Saxena, Orthopaedic Surgeon (Co-supervised with Prof Grant Burgess and Prof Mike Reed)
Recent Alumini:
Horeyah Abdalkrim (Royal Saudi Arabian Government PhD Studentship)
Becky Kildani (Barbour Foundation PhD Studentship)
David Bulmer (Postdoc, BBSRC, MRC)
Michail Karavolos (Postdoc, BBSRC, MRC)
Sonya Carnell (Postdoc, Italian CF Trust)
Wei Chen (Postdoc, China Scholarship Council)
Nancy Liang (Postdoc, China Scholarship Council)
Anne Doble (MRC PhD Studentship)
Lubna Kharraz (Ford Foundation of America, PhD Studentship)
Hannah Spencer (BBSRC PhD Studentship)
Rerngwit Boonyom (Royal Thai Government Studentship)
Other Expertise
Molecular and Cellular Biology of Microbial Pathogens
Competitive Interactions of Pathogens with Microbiota
Vaccine Discovery and Novel Delivery Platforms
Infection and Immunity
Microbial Biofilms and Infections
Research Roles
Principle Investigator
Director, Infectious Diseases Facility
Postgraduate Supervision
Prospective International students, as well as UK students, with broad interests in Molecular and Cellular Microbiology are particularly encouraged to apply for doctoral degrees (PhD).
Esteem Indicators
Member of the Medical Research Council (MRC) Infections and Immunity Board College of Experts (2009-13)
Funding
Heraeus Medical (GmbH)
MRC-BBSRC Funded BactiVac Scheme
Medical Research Council (MRC)
Biotechnology and Biological Sciences Research Council (BBSRC)
Wellcome Trust
Newcastle Healthcare and NHS Hospitals Special Trustees Charity
Patents
Four International Patents Awarded in the areas of "Biotechnology, Vaccine Discovery and Delivery"
Teaching
Undergraduate teaching include the following modules:
BMS2002: Cell Signalling
MIC2025: Bacterial Interactions with Human Hosts and
the Immune System in Human Disease
MIC2027: Parasitic and Viral Diseases (Module Leader)
MIC3043: Research in Medical Microbiology and Immunology
MIC3027: Bacterial Pathogenicity and Disease
MIC3046: Pathogenic Viruses, Protozoa, and Fungi (Module Leader)
CMB3000: Research Projects
Postgraduate teaching:
PhD Supervisor
PhD Examiner
Publications
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Articles
- Jackson RM, Hatton CF, Spegarova JS, Georgiou M, Collin J, Stephenson E, Verdon B, Haq IJ, Hussain R, Coxhead JM, Mudhar H-S, Wagner B, Hasoon M, Davey T, Rooney P, Khan A, Ward C, Brodlie M, Haniffa M, Hambleton S, Armstrong L, Figueiredo F, Queen R, Duncan CJ, Lako M. Conjunctival epithelial cells resist productive SARS-CoV-2 infection. Stem Cell Reports 2022, 17(7), 1699-1713.
- Hatton CF, Botting RA, Duenas ME, Haq IJ, Verdon B, Thompson BJ, Spegarova JS, Gothe F, Stephenson E, Gardner AI, Murphy S, Scott J, Garnett JP, Carrie S, Powell J, Khan CMA, Huang L, Hussain R, Coxhead J, Davey T, Simpson AJ, Haniffa M, Hambleton S, Brodlie M, Ward C, Trost M, Reynolds G, Duncan CJA. Delayed induction of type I and III interferons mediates nasal epithelial cell permissiveness to SARS-CoV-2. Nature Communications 2021, 12(1), 7092.
- Carnell SC, Perry JD, Borthwick L, Vollmer D, Biboy J, Facchini M, Bragonzi A, Silipo A, Vergunst AC, Vollmer W, Khan ACM, De Soyza A. Targeting the bacterial cytoskeleton of the Burkholderia cepacia complex for antimicrobial development: A cautionary tale. International Journal of Molecular Sciences 2018, 19(6), 1604.
- Bulmer DM, Kharraz L, Grant AJ, Dean P, Morgan FJ, Karavolos MH, Doble AC, McGhie EJ, Koronakis V, Daniel RA, Mastroeni P, Khan CMA. The bacterial cytoskeleton modulates motility, type 3 secretion, and colonization in Salmonella. PLoS Pathogens 2012, 8(1), e1002500.
- Staniewicz L, Donald AM, Stokes DJ, Thomson N, Sivaniah E, Grant A, Bulmer D, Khan A. The Application of STEM and In situ Controlled Dehydration to Bacterial Systems Using ESEM. Scanning 2012, 34(4), 237-246.
- Nicholson A, Perry JD, James AL, Stanforth SP, Carnell S, Wilkinson K, Anjam Khan CM, De Soyza A, Gould FK. In vitro activity of S-(3,4-dichlorobenzyl)isothiourea hydrochloride and novel structurally related compounds against multidrug-resistant bacteria, including Pseudomonas aeruginosa and Burkholderia cepacia complex. International Journal of Antimicrobial Agents 2012, 39(1), 27-32.
- Karavolos MH, Bulmer D, Spencer H, Rampioni G, Schmalen I, Baker S, Pickard D, Gray J, Fookes M, Winzer K, Ivens A, Dougan G, Williams P, Khan CMA. Salmonella Typhi sense host neuroendocrine stress hormones and release the toxin haemolysin E. EMBO Reports 2011, 12(3), 252-258.
- Boonyom R, Karavolos MH, Bulmer DM, Khan CM. Salmonella pathogenicity island 1 (SPI-1) type III secretion of SopD involves N- and C-terminal signals and direct binding to the InvC ATPase. Microbiology 2010, 156(6), 1805-1814.
- Spencer H, Karavolos MH, Bulmer DM, Aldridge P, Chhabra SR, Winzer K, Williams P, Khan CMA. Genome-Wide Transposon Mutagenesis Identifies a Role for Host Neuroendocrine Stress Hormones in Regulating the Expression of Virulence Genes in Salmonella. Journal of Bacteriology 2010, 192(3), 714-724.
- Perrett CA, Karavolos MH, Humphrey S, Mastroeni P, Martinez-Argudo I, Spencer H, Bulmer D, Winzer K, McGhie E, Koronakis V, Williams P, Khan CMA, Jepson MA. LuxS-Based Quorum Sensing Does Not Affect the Ability of Salmonella enterica Serovar Typhimurium To Express the SPI-1 Type 3 Secretion System, Induce Membrane Ruffles, or Invade Epithelial Cells. Journal of Bacteriology 2009, 191(23), 7253-7259.
- Ierano T, Silipo A, Sturiale L, Garozzo D, Bryant C, Lanzetta R, Parrilli M, Aldridge C, Gould FK, Corris PA, Khan CMA, De Soyza A, Molinaro A. First structural characterization of Burkholderia vietnamiensis lipooligosaccharide from cystic fibrosis-associated lung transplantation strains. Glycobiology 2009, 19(11), 1214-1223.
- Ieranò T, Silipo A, Sturiale L, Garozzo D, Brookes H, Khan CM, Bryant C, Gould FK, Corris PA, Lanzetta R, Parrilli M, De Soyza A, Molinaro A. The structure and proinflammatory activity of the lipopolysaccharide from Burkholderia multivorans and the differences between clonal strains colonizing pre and posttransplanted lungs. Glycobiology 2008, 18(11), 871-881.
- Karavolos MH, Bulmer DM, Winzer K, Wilson M, Mastroeni P, Williams P, Khan CMA. LuxS affects flagellar phase variation independently of quorum sensing in Salmonella enterica serovar typhimurium. Journal of Bacteriology 2008, 190(2), 769-771.
- McKelvie ND, Khan SA, Karavolos MH, Bulmer DM, Lee JJ, DeMarco R, Maskell DJ, Zavala F, Hormaeche CE, Anjam Khan CM. Genetic detoxification of an aroA Salmonella enterica serovar Typhimurium vaccine strain does not compromise protection against virulent Salmonella and enhances the immune responses towards a protective malarial antigen. FEMS Immunology and Medical Microbiology 2008, 52(2), 237-246.
- Karavolos MH, Spencer H, Bulmer DM, Thompson A, Winzer K, Williams P, Hinton JCD, Anjam Khan CM. Adrenaline modulates the global transcriptional profile of Salmonella revealing a role in the antimicrobial peptide and oxidative stress resistance responses. BMC Genomics 2008, 9(1), 458.
- Silipo A, Molinaro A, Ierano T, De Soyza A, Sturiale L, Garozzo D, Aldridge C, Corris PA, Khan CMA, Lanzetta R, Parrilli M. The complete structure and pro-inflammatory activity of the lipooligosaccharide of the highly epidemic and virulent gram-negative bacterium Burkholderia cenocepacia ET-12 (strain J2315). Chemistry - A European Journal 2007, 13(12), 3501-3511.
- Liu W-T, Karavolos MH, Bulmer DM, Allaoui A, Hormaeche RDCE, Lee JJ, Anjam Khan CM. Role of the universal stress protein UspA of Salmonella in growth arrest, stress and virulence. Microbial Pathogenesis 2007, 42(1), 2-10.
- Karavolos MH, Wilson M, Henderson J, Lee JJ, Khan CMA. Type III secretion of the Salmonella effector protein SopE is mediated via an N-terminal amino acid signal and not an mRNA sequence. Journal of Bacteriology 2005, 187(5), 1559-1567.
- De Soyza A, Ellis CD, Khan CMA, Corris P, Demarco de Hormaeche R. Burkholderia Cenocepacia Lipopolysaccharide, Lipid A and Proinflammatory Activity. American Journal of Respiratory and Critical Care Medicine 2004, 170(1), 70-77.
- Ellis CD, Lindner B, Khan CMA, Zahringer U, Demarco De Hormaeche R. The Neisseria gonorrhoeae lpxLII gene encodes for a late-functioning lauroyl acyl transferase, and a null mutation within the gene has a significant effect on the induction of acute inflammatory responses. Molecular Microbiology 2001, 42(1), 167-181.
- Lee JJ, Sinha KA, Harrison JA, Demarco De Hormaeche R, Riveau G, Pierce RJ, Capron A, Wilson RA, Khan CMA. Tetanus toxin fragment C expressed in live Salmonella vaccines enhances antibody responses to its fusion partner Schistosoma haematobium glutathione S-transferase. Infection and Immunity 2000, 68(5), 2503-2512.
- Heal KG, McConkey GA, Hormaeche CE, Hollingdale MR, Khan CMA, Taylor-Robinson AW. Expression of TetC fusion proteins from Salmonella in a gaseous environment that models conditions found in mammalian tissues. BioTechniques 2000, 28(2), 228-232.
- McNeill HV, Sinha KA, Hormaeche CE, Lee JJ, Khan CMA. Development of a nonantibiotic dominant marker for positively selecting expression plasmids in multivalent Salmonella vaccines. Applied and Environmental Microbiology 2000, 66(3), 1216-1219.
- CHATFIELD SN, ROBERTS M, DOUGAN G, HORMAECHE C, KHAN CMA. THE DEVELOPMENT OF ORAL VACCINES AGAINST PARASITIC DISEASES UTILIZING LIVE ATTENUATED SALMONELLA. PARASITOLOGY 1995, 110, S17-S24.
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Book Chapter
- Karavolos MH, Khan CMA. Multidirectional Chemical Signalling Between Mammalian Hosts, Resident Microbiota, and Invasive Pathogens: Neuroendocrine Hormone-Induced Changes in Bacterial Gene Expression. In: Microbial Endocrinology: The Microbiota-Gut-Brain Axis in Health and Disease. New York: Springer, 2014, pp.241-253.
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Conference Proceedings (inc. Abstracts)
- Macfarlane JG, Dorward DA, Lucas CD, Scott JA, Ruchaud-Sparagano MH, Khan CMA, Rossi AG, Simpson AJ. Src/bcr-abl Inhibition with Dasatinib in Sterile and Non-Sterile Acute Lung Inflammation. In: British Thoracic Society Winter Meeting 2014. 2014, London: BMJ Publishing Group.
- Carnell SC, Perry JD, Vollmer D, Biboy J, Facchini M, Bragonzi A, Vergunst A, Vollmer W, Khan CMA, De Soyza A. Targeting the bacterial cytoskeleton of CF pathogens for antimicrobial development – A cautionary tale?. In: British Thoracic Society Winter Meeting. 2013, London, UK: BMJ Publishing Group.
- Macfarlane JG, Ruchaud-Sparagano MH, Scott JA, Bulmer DA, Khan CMA, Simpson AJ. Src Kinase Inhibition Attenuates Neutrophil Degranulation Without Impairing Bacterial Killing: A Possible Therapeutic Strategy for Acute Lung Injury?. In: British Thoracic Society Winter Meeting. 2013, London, UK: BMJ Publishing Group.
- Carnell SC, Biboy J, Cerardi G, Ville B, Deleuse C, Samain R, Vollmer D, Khan CMA, Gray J, Vollmer W, De Soyza A. Pathogen associated molecular patterns in cystic fibrosis pathogens: Analysis of peptidoglycan structure. In: British Thoracic Society Winter Meeting. 2013, London, UK: BMJ Publishing Group.
- Carnell SC, Perry JD, Khan CMA, De Soyza A. The bacterial cytoskeleton-A new antimicrobial target in cystic fibrosis pathogens?. In: Thorax: British Thoracic Society Winter Meeting. 2010, Westminster, UK: BMJ Group.
- Aldridge PD, Gray MA, Hirst BH, Khan CMA. Who's talking to whom? Epithelial-bacterial pathogen interactions. In: International Symposium on Epithelial-Bacterial Pathogen Interactions. 2004, Newcastle upon Tyne, UK: Molecular Microbiology: Wiley-Blackwell.
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Editorial
- Doble AC, Bulmer DM, Kharraz L, Karavolos MH, Khan CMA. The function of the bacterial cytoskeleton in Salmonella pathogenesis. Virulence 2012, 3(5), 446-449.
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Notes
- Karavolos MH, Williams P, Khan CMA. Interkingdom crosstalk Host neuroendocrine stress hormones drive the hemolytic behavior of Salmonella typhi. Virulence 2011, 2(4), 371-374.
- Karavolos MH, Roe AJ, Wilson M, Henderson J, Lee JJ, Gally DL, Khan CMA. Erratum: Type III secretion of the Salmonella effector protein SopE is mediated via an N-terminal amino acid signal and not an mRNA sequence (Journal of Bacteriology (2005) 187, 5 (1559-1567)). Journal of Bacteriology 2005, 187(15), 5505-5505.
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Reviews
- Khan CMA. The Dynamic Interactions between Salmonella and the Microbiota, within the Challenging Niche of the Gastrointestinal Tract. ISRN Microbiology 2014, 2014, 846049.
- Karavolos MH, Winzer K, Williams P, Khan CM. Pathogen espionage: multiple bacterial adrenergic sensors eavesdrop on host communication systems. Molecular Microbiology 2013, 87(3), 455-465.