AFC Winter 2005

January 2005

Scientific Programme

Session 1
What do microarrays really tell us about M. tuberculosis?
Neil Stoker

Evaluation of TB vaccines in guinea pigs – challenges and solutions to improve discrimination between candidates
Ann Williams, Hatch GJ, Clark SO, Gooch K, Hatch K, Hall GA, Marsh PD. (submitted by J. Ivanyi)

Ancient DNA analysis of cases of lepromatous leprosy from the archaeological record
C L Watson, S Mays D N J Lockwood & G M Taylor

Role of Mycobacterium tuberculosis PGL derivative, pHBAD-II, in innate immunity.
Ruth Griffin, Pearline Benjamin, Steven Coade, Germain Puzo, Brigitte Gicquel, Roger Buxton, Douglas Young, Mary Jackson, Ricardo Tascon Douglas Lowrie

Investigation of rifampicin resistance in isoniazid resistant strains of Mycobacterium tuberculosis isolated during an outbreak in North London
C. Jenkins, A. Claxton, R.J. Shorten, T.D. McHugh and S.H. Gillespie

Vitamin D: a double-edged sword in anti-mycobacterial immunity?
Martineau AR, Newton SM, Wilkinson KA, Norman AW, Griffiths CJ, Wilkinson RJ

Session 2
Effectiveness and acceptability of TB screening: a randomised trial and qualitative study
Chris Griffiths, Pat Sturdy, Penny Brewin, Meg McDonald, Adrian Martineau, Sandra Eldridge, Gene Feder, Miriam Beeks, Anna Jones, Graham Bothamley, Moira Kelly, Jean Ramsay, Ali Zumla

Disseminated Mycobacterium TB infection due to functional IFN-gamma deficiency
SL Seneviratne, R Doffinger , J McFarlane, L Ceron-Gutierrez, MR Amel Kasipaz, A Robbins, P Powell, DS Kumararatne, RJ Powell

A FHA domain-containing phospho-dependent signalling pathway of Mycobacterium tuberculosis is required for virulence in mice
Juliet M. Curry, Rachael Whalan, Debbie M. Hunt, Kalpesh Gohil, Molly Strom, Lisa Rickman, M. Joseph Colston, Stephen J. Smerdon and Roger S. Buxton

Regulating gene expression in mycobacteria. All in the ‘mind’
Marian C. J. Blokpoel, Helen Murphy, Ronan O’Toole, Siouxsie Wiles, Graham R. Stewart, Douglas B. Young, Brian D. Robertson

Control of M. bovis in the presence of a wildlife reservoir
Dirk Pfeiffer (submitted by Neil Stoker)

AFC Summer 2004

July 2004

Scientific Programme

Session 1

Methionine- the preferred sulphur source for pathogenic mycobacteria? Refining the genomic information with metabolic investigations
Paul R Wheeler, Nicholas G Coldham, Lisa Keating, Stephen V Gordon, Esen E Wooff, Tanya Parish and R Glyn Hewinson. VLA

Effect of prednisolone treatment on cytokine expression in leprosy patients with type 1 reaction (T1R)
Anna K Andersson, Mehervani Chaduvula, Sara Atkinson, Saroj Khanolkar-Young, Martin Holland, Suman Jain, Lavanya Suneetha, Sujai Suneetha and Diana N J Lockwood. London School of Hygiene and Tropical Medicine

Characteristic genomic deletion pattern in clinical isolates of M. tuberculosis from South Asian patients
M. Carmen Menendez, Rahizan Issa, Roger S. Buxton, Evangelos Stavropoulos, Peter M. Hawkey and M. Joseph Colston

The role of oxidative stress in Mycobacterium tuberculosis evolution
O’ Sullivan D, McHugh TD, Gillespie SH. Royal Free & University College London Medical School

IFN gamma responses in young adults from the UK BCG programme: The first SSI BCG vaccinated cohort
Patricia Gorak-Stolinska, Rosemary E. Weir, Maeve Lalor, Rose Blitz, Nisha Faruk, Paul E.M. Fine, Hazel M. Dockrell. London School of Hygiene and Tropical Medicine

DGAT, FATP and FACS, does the TAG team do it for M tuberculosis in vivo?
Natalie Garton, University of Leicester

Session 2

An investigation of the phenotype of an outbreak strain of M. tuberculosis.
SM Newton, KA Wilkinson, RJ Smith, GR Stewart, JR Wain, RA Stabler, P Butcher, J Shafi, P Andrew, M Barer, RJ Wilkinson Imperial College London

Involvement of a specific phospholipase D isoform in the ATP-mediated killing of intracellular mycobacteria
Lorna Forse, Cheuk Li and Tony Lammas. University of Birmingham

IL-4 delta 2 and Th2 cytokines in human Pulmonary Tuberculosis
K Dheda, JF Huggett, MA Johnson, A Zumla and G Rook. UCL and Royal Free Medical School

Population genetics of Mycobacterium bovis field strains from cattle in Iran
Tadayon, Keyvan, Forbes, Ken. University of Aberdeen

Did mutational ablation of a CRP-like global regulator contribute to the attenuation of BCG? Claire Spreadbury and Mark Pallen

AFC Winter 2004

January 2004

Scientific Programme

Session 1

Stationary phase gene expression of Mycobacterium tuberculosis following a progressive nutrient depletion: a model for persistent organisms?
Tobias Hampshire, Shamit Soneji, Joanna Bacon, Brian W James, Jason Hinds, Philip D Marsh and Philip D Butcher

Mycobacterium bovis and the Atkins diet
Lisa Keating, Paul R Wheeler, Huma Mansoor, Jackie Inwald, R Glyn Hewinson and Stephen V Gordon

The effect of treatment of latent tuberculosis infection on the frequency of M. tuberculosis specific IFN-γ producing cells
Wilkinson, KA, Kon, OM Davidson, RN, Pasvol, G., Wilkinson, R.J

How do the Rpf proteins stimulate bacterial growth?
G Mukamolova, A Ravagnani, C Finan, R Shleeva, D I Young, O A Turapov, A S Kaprelyants & M Young

Gene expression patterns in blood discriminate individuals with active, cured, recurrent or latent tuberculosis
R Mistry, CL Clayton, J Cliff, N Beyers, Y Mohamed, PA Wilson, DM Wallace, P van Helden, K Duncan and PT Lukey

Treatment of tuberculosis: time for a new paradigm?
Stephen Gillespie

Session 2

The modulation of bovine T-cell responses by glycans of the Mycobacterium bovis antigen MPB83
AO Whelan, RG Hewinson and HM Vordermeier

Whole genome analysis of a mutant M. tuberculosis informs rational antigen discovery: Rv0251c (Acr 2) is a major target of the early human T cell response
Stewart GR, Wilkinson KA, Horner K, Newton, SM, Wain, JR, Murphy H, Dickson SJ, Young DB, Wilkinson RJ

The signal transducing activity of the M. tuberculosis chaperonin 60.1 protein is associated with the equatorial domain
Peter Tormay, Sajeda Meghji, Jon Mesher, Brian Henderson and Anthony R. M. Coates

Fructose bisphosphatase in the Mycobacterium tuberculosis complex – the missing link in central metabolism
Farah Movahedzadeh, Stuart Rison, Neil Stoker and Paul Wheeler

AFC Summer 2003

Held at Leicester University

July 2003

Scientific Programme

Special symposium – The Leicester Crown Hills School TB Outbreak
A public health perspective
Philip Monk. East Midlands, Health Protection team

A clinical perspective
Wren Hoskins. Consultant Paediatrician

Immune responses to the outbreak strain
Ajit Lalvani. Oxford University

Applied genomics of the outbreak strain
Mike Barer. Leicester University

Session 1 – Dedicated to the memory of Jo Colston
Functional activation of dendritic cells in response to Mycobacterial infection
E. Roy, M. Yang, J. Downey, J.C. Ferraz, S. Coade, B. stockinger, M. J. Colston and R. E. Tascon

The Influence of reduced oxygen availability on virulence and gene expression in M.
tuberculosis
Joanna Bacon, Brian W. James, Kim A. Morley, Lorenz Wernisch, Ann Williams, Graham J. Hatch, Kristian Birchall, Joseph A. Mangan, Jason Hinds, Philip D. Butcher and Philip D. Marsh

A revised role for NusA in rrn anti-termination
K. Arnvig, S. Cochrane, B. Gopal, S. Pennell and M.J. Colston

Could we ever take M. tuberculosis out of the Cat3 laboratory?
Farah Movahedzadeh and Neil Stoker

The role of DNA repair genes in Mycobacterium tuberculosis pathogenesis
Lucinda Rand and Elaine Davis

Session 2
The Phase I Evaluation of a Candidate TB Vaccine, MVA85
Helen McShane, Ansar Pathan, Adrian Hill

Shedding light on the ephemeral activity of resuscitation promoting factor: use of
bioluminescence to measure activity
Angharad Davies, Brian Henderson, John Ward, Mike Young & Stephen Gillespie

Immune profiling of leprosy and tuberculosis patients to 15-mer peptides of M. leprae
and M. tuberculosis GroES in a BCG vaccinated area: Implications for development of
vaccine and diagnostic reagents
R. Hussain, F. Shahid, S. Zafar, M. Dhojki, H. M. Dockrell

Functional Genomics of Mycobacterium tuberculosis complex proteins linked to
tuberculosis pathogenesis and protective immunity
Philip S Renshaw, Marieke J Bloemink, Ellen Denten, Kirsten Lightbody, Stephen V Gordon, R Glyn Hewinson, Geoff Kelly, Thomas A Frenkiel, Richard A Williamson and Mark D Carr

Session 3
Sensor Sensibility: the input domains of Mycobacterial 2-component system sensor
proteins
Stuart Rison and Neil Stoker

Selective susceptibility to disseminated mycobacterial infections caused by auto
antibodies to gamma interferon
Doffinger R, Helbert M, Longhurst H,Barcenas-Morales G, Barnes N, Kumararatne D

Description of a new M. tuberculosis lineage, Kilimanjaro 1: defining the boundaries.
Rob Shorten, Tim McHugh, Sarah Batt, Roly Gosling, Esther Kanduma & Stephen
Gillespie

Early mycobacterial infection of mouse lung dendritic cells in vivo
Rajko Reljic, Caterina Di Sano, Carol Crawford, Francesco Dieli, Stephen Challacombe1 and Juraj
Ivanyi

Cytochrome P450 systems in M. tuberculosis – novel targets for azole-based drugs.
Andrew Munro

Signature gene expression profiles discriminate between isoniazid, thiolactomycin and
triclosan treated Mycobacterium tuberculosis
Joanna C. Betts, Alistair McLaren, Mark G. Lennon, Fiona M. Kelly, Pauline T. Lukey, Steve J. Blakemore and Ken Duncan

AFC Winter 2003

January 2003

Scientific Programme

Session 1

TB imaging- a new way forward?
Satya Das, KE Britton, DW Wareham (introduced by Tanya Parish)

The SenX3 RegX3 two component regulatory system of Mycobacterium tuberculosis.
Gretta Roberts, Debbie Smith, Jo Betts, Neil Stoker, Tanya Parish

Increased mRNA encoding IL-4d2 and IL-4 in unstimulated peripheral blood mononuclear cells from those TB contacts whose cells release IFN in response to ESAT-6
Helen Fletcher, Roger Brookes, Patrick Owiafe, Philip Hill, Mark Doherty, Graham Rook, Alimuddin Zumla & the VACSELstudy group

The cAMP receptor protein (CRP) of Mycobacterium tuberculosis: effect of a null mutation in this global regulator
Lisa Rickman, Jeffrey Green, Colin Scott, Jo Colston and Roger Buxton

Naturally acquired sensitivity to PPDs of environmental mycobacteria among UK school children^.
Rosemary Weir, Paul Fine, Bernadette Nazareth, Sian Floyd, Gillian Black, Carolynne Stanley, Lyn Bliss, Keith Branson, and Hazel M. Dockrell

Is there a major endemic of tuberculoid leprosy in Central America?
John L Stanford and Helen D Donoghue on behalf of the Nicaragua Study Group Leprosy in Nicaragua

Session 2

What pathogenic mycobacteria want- amino acid biosynthesis and availability in the host.
Paul Wheeler, Lisa Keating, Esen Wooff, Steve Gordon, Tanya Parish and Glyn Hewinson

Roles of Serine/Threonine protein kinases in M. tuberculosis pathogenicity.
K. G. Papavinasasundaram, Bosco H. Y. Chan, Elaine O. Davisand M. Joseph Colston

Induction by Mycobacterium vaccae and its components of regulatory mechanisms involving IL-10 and TGF-β that suppress allergic responses
L. Rosa Brunet, C. Zuany-Amorim, E. Sawicka, C. Manlius, A. Le Moine, V. Adams, B. Palmer, J. Hunt, G.S. Besra, C. Walker, G. Rook

Mycobacterium tuberculosis sigJ knockout alters sensitivity of slow- growing bacteria to hydrogen peroxide
Yanmin Hu, Sharon Kendall, Neil Stoker, Anthony Coates

Effector memory CD8 T cells are associated with long-term immune control of M. tuberculosis.
Kazi F, Prakash M, Ewer K, Waller S, Varia H, Pasvol G & Lalvani A

Koch’s Bacillus – A look at the first isolate of M. tuberculosis from a modern perspective.
Taylor GM, Stewart GR, Cooke M, Ladva, S, Young DB

AFC Summer 2002

July 2002

Scientific Programme

Session 1
Mycobacteria versus Burkholderia
Eshwar Mahenthiralingam. University of Cardiff

The ESAT-6/WXG100 superfamily–and a new mycobacterial secretion system?
Mark J. Pallen

Expression of Toll-like receptors in the lungs of patients with pulmonary tuberculosis
Pauline T. Lukey*, Gael Fenhalls#, Ginette R. Webb*, Liesel Stevens-Muller#, Juanita Bezuidenhout#, Gillian Amphlett* and Ken Duncan*, *GlaxoSmithKline, Stevenage, UK and #University of Stellenbosch, Cape Town, South Africa

Session 2
Heterologous prime-boost immunisation strategies using plasmid DNA and BCG vaccination against tuberculosis
Ferraz J. C. Jr., Colston M. J., Espitia C., Yang M., Coade S., Raynaud C., Lowrie D. B., and Tascon R. E

Characterisation of a Mycobacterium tuberculosis H37Rv transposon library reveals insertions in 351 open reading frames and mutants with altered virulence
Ruth A. McAdam*, Selwyn Quan*, Debbie A. Smith#, Stoyan Bardarov+, Joanna C. Betts*, Fiona C. Cook*, Elizabeth U. Hooker*, Alan Lewis*, Peter Woollard*,Martin J. Everett*, Pauline T. Lukey*, Gregory J. Bancroft#, William R. Jacobs Jr+, and Ken Duncan*; *GlaxoSmithKline, #London School Of Hygiene & Tropical Medicine and +Albert Einstein College of Medicine

From CTL to TRL to MRU: The history of the reference laboratory
Tony Jenkins

Session 3
Are the Rpf family of growth factors essential for bacterial multiplication?
G V Mukamolova, O A Turapov, D I Young, C L Finan, A S Kaprelyants, D B Kell & M Young

Hsp65 DNA Vaccination in a mouse aerosol challenge system
B Walker, A Thiobhani, M Addawe, NIBSC

Phospho-threonine-binding FHA domains in mycobacterial proteins–neglected players in the phospho-signalling game?
Mark J. Pallen, Arshad M. Khan, Roy Chaudhuri

Session 4
Modification of nat, the gene encoding arylamine N-acetyltransferase which acetylates isoniazid, affects the growth and cellular morphology of mycobacteria
Sanjib Bhakta, Anna Upton, Frederique Pompeo, Mark Payton, Edith Sim, Tanya Parish

Operomics – towards an operon map of M. tuberculosis
Neil Stoker

Rapid Genomic and Biological Characterisation Of The Leicester School Tuberculosis Outbreak Strain
Jamila Shafi. Department of Microbiology and Immunology, University of Leicester, UK

AFC Summer 2001

Held at Newcastle University

July 2001

Newcastle Mini symposium

New antimycobacterial agents, related to thiolactomycin
David E. Minnikin

Galactan biosynthesis in Mycobacterium tuberculosis: Identification of a bifunctional UDP-galactofuranosyltransferase
Lynn Dover

Biochemical characterisation of acyl carrier protein (AcpM) and  malonyl-CoA:AcpM transacylase (mtFabD), two major components of  Mycobacterium tuberculosis fatty acid synthase II
K. Madhavan Nampoothiri:

Ppm1, a prenol monophospho-mannose synthase from Mycobacterium tuberculosis
Gurdyal S. Besra

Session 1

Construction  and application of a gene-specific whole genome DNA microarray for M. tuberculosis
J Hinds¹, JA Mangan¹, KG Laing¹, H Al-Ghusein¹, NG Stoker², JK Vass³, RS Buxton⁴, MJ Colston⁴, PD Butcher¹. ¹St George’s Hospital Medical School, London. ²London School of Hygiene and Tropical Medicine, London. ³Beatson Institute, Glasgow. ⁴NIMR, Mill Hill, London

Molecular investigation of the role the 34 kDa protein plays in the virulence of M. a. partatuberculosis
Darragh Heaslip, Karen Stevenson, Johnjoe McFadden* and J Michael Sharp.  Moredun Research Institute and *University of Surrey

The molecular analysis of Mycobacterium bovis (MTB) DNA from a family of 18th Century Hungarians
Fletcher HA, Donoghue HD, Taylor  GM, van der Zander AGM and Spigelman M. Department of Medical Microbiology, UCL

Session 2

Inositol metabolism in mycobacteria: Genetic and structural studies
Neil Stoker and Farah Movahedzadeh, LSHTM

CD4+ and CD8+ T cells kill intracellular M. tuberculosis by a perforin and FAS/FASL independent mechanism
DH Canaday*, RJ Wilkinson¹*, Q Li*, CV Harding¹, RF Silver*, WH Boom*. ¹Wellcome Centre for Clinical Tropical Medicine, Imperial College School of Medicine, London.  *Division of Infectious Diseases, Department of Pathology, Division of Pulmonary and Critical Care Medicine, Case Western Reserve University School of Medicine and University Hospitals of Cleveland, Ohio.

What is the function of OmpATb, a pore-forming protein of M. tuberculosis?
Philip Draper, Catherine Raynaud, Jo Colston and Richard Speight (NIMR, Mill Hill)

Session 3

What is Mycobacterium microti? Analysis of genomic variation using microarrays
C Cunha Frota, M J Colston, L Rickman, D Hunt R Buxton, NIMR, Mill Hill.  P Butcher, J Hinds St George’s Medical School, London.  D Van Soolingen, RIVM, Bilthoven, The Netherlands

A family of autocrine growth factors in Mycobacterium tuberculosis
GV Mukamolova, OA Turapov, DI Young, SL Hardy, AS Kaprelyants, DB Kell, M Young.  Institute of Biological Sciences, University of Wales, Aberystwyth

How does M. tuberculosis ensure efficient transcription of ribosomal RNA?
Kristine Arnvig, B. Gopal, R A Cox, K G Papavinasasundaram, M J Colston. NIMR, Mill Hill, London

A large outbreak of tuberculosis in a Leicester school
D. Modha, P Monk, L Coole, G Bryant.  Dept of Public Health, Leicestershire Health Authority

AFC Winter 2001

Held at The Royal Free Hospital, London

January 12^th 2001

Scientific Programme

Session 1

The Molecular Epidemiology of TB in London 1995-1997
Tim McHugh, Royal Free Hospital, on behalf of the Principal Investigators of the London TB study Group

Effect of BCG vaccination on IFN? responses to mycobacterial antigens in UK schoolchildren as
compared to Malawian young adults : a potential correlate of vaccine–induced protective
immunity ?
R.E. Weir¹, G. F. Black^1,2, P.E.M. Fine¹ and H.M. Dockrell¹. ¹Dept of Infectious and Tropical Diseases, LSH&TM, Keppel Street, London WC1E 7HT, ²Karonga Prevention Study, PO Box 46, Chilumba, Malawi

Effect of oxygen availability on the physiology and pathogenicity of Mycobacterium tuberculosis
Brian James and Philip Marsh, CAMR, Salisbury

Environmental survival of mycobacteria
Stephanie Taylor, Frans de Leij, Jeremy Dale, Molecular Microbiology Group, School of Biological Sciences, University of Surrey

The search for environmental mycobacteria in Karonga district, northern Malawi
Ben Chilima, Paul Fine and Penny Hirsch. London School of Hygiene & Tropical Medicine; IACR-
Rothamsted

The effect of stimulation of antigen presentation on M. tuberculosis infection
Stephen Jolles, Gerry Klaus, Ricardo Tascon and Jo Colston, The National Institute for Medical Research, London

Session 2

Deciphering the code of a mycobacterial enigma: understanding physiology from the
Mycobacterium leprae genome
P. Wheeler¹ and ST Cole². ¹TB Research Group, VLA Weybridge, ²Institut Pasteur, France

ATP-mediated killing of intracellular mycobacteria by macrophages is a P2X7-dependent process
inducing bacterial death by phagosome-lysosome fusion
Ian P. Fairbairn, David A. Lammas, Carmel B. Stober, Dinakantha S. Kumararatne. MRC Centre for Immune Regulation, Birmingham Medical School, Birmingham University

Genomic mutations and IS6110 in M. tuberculosis: Man as a model system?
Hasan Yesilkya, Jeremy Dale, Ken Forbes Medical Microbiology, Aberdeen University and Molecular
Microbiology Group, School of Biological Sciences, University of Surrey

Mycobacteria and the control of blood flow
Gerard Stansby, Christoph Berwanger, Yiu Che Chan and John Stanford. Department of Vascular Surgery, University of Newcastle upon Tyne and the Department of Medical Microbiology, RFUCMS, London

Widespread Occurrence of Mycobacterium tuberculosis-DNA from 18th-19th Century Hungarians
Helen Fletcher¹, Helen D. Donoghue¹, John Holton¹, Ildicó Pap² and Mark Spigelman¹, ¹Department of Medical Microbiology, University College London, London W1P 6DB, UK; ²Anthropology Department, Hungarian Natural History Museum, Ludovika tér 2, Budapest, Hungary H-1083

AFC Summer 2000

Held at The John Radcliffe Hospital, Oxford

July 9th 2000

Scientific Programme

Session 1

A mechanism for CD8+ T cell mediated suppression of intracellular mycobacterial growth
R Brookes, H McShane, N Goonetilleke, A Lalvani, AA Psthan, DA Price, GM Griffiths & A Hill.  Oxford University

OmpATb – a pore-forming protein of M. tuberculosis and how it may be regulated
R Speight & P Draper. NIMR

An increase in expression of a M. tuberculosis mycolyl transferase gene (fbpB) occurs early after infection of human monocytes
RJ Wilkinson¹²³, LE DesJardin², BM Gibson², KA Wilkinson¹, D Poleman¹, RA Kanost¹, KD Eisenach², Z Toossi².  ¹Division of Infectious Diseases, Case Western Reseve University, Cleveland, Medical Research Service. ²JL McClellan Memorial Veterans’ Administration Hospital, Little Rock. ³Wellcome Centre for Clinical Tropical Medicine, Imperial College of Medicine, Northwick Park Hospital

Genetic Transformation of Mycobacterium paratuberculosis
S Thorne & JJ McFadden.  University of Surrey

Role of heat shock proteins in inflammation: M. tuberculosis chaperonin 60.1 (hsp60) is a more potent cytokine-stimulator than chaperonin 60.2 (hsp65) and contains a cryptic CD14-binding domain
JC Lewthwaite, ARM Coates, S Kahn, M Singh, P Mascagni, S Poole, M Roberts & B Henderson.  Eastman Dental Institute and St George’s Hospital Medical School

The use of recombinant viruses as tuberculosis vaccines
N Goonetilleke, R Anderson, H McShane, S Gilbert, R Brookes & A Hill.  Oxford University

Session 2

Crystal Structure of Mycobacterium tuberculosis Chaperonin 10
M Roberts, AR Coker, ARM Coates and SP Wood.  St George’s Hospital Medical School and Southampton University

Growth control and dormancy in Mycobacterium smegmatis
R Wright, J Dickinson, S Thorne, M Bushell & JJ McFadden.  University of Surrey

Protection against tuberculosis in a prime-boost regime is mediated by one CD4+ and one CD8+ T cell epitope
H McShane, S Behboudi, N Goonetilleke, S Gilbert, R Brookes & A Hill.  Oxford University

Comparative studies of defined skin test antigens in M. bovis infected guinea pigs and cattle
AO Whelan, HM Vordermeier & RG Hewinson.  VLA Weybridge

Stressed up, Messed up: De-regulation of HSP70 response in Mycobacterium tuberculosis
G Stewart, V Snewin, P Tormay, P O’Goara, M Goyal, I Brown & DB Young.  Imperial College of Medicine at St Mary’s Hospital