Networking

Existing networks and linkages
Both nodes of the CBTBR are involved in wide collaborative networks that involve TB researchers and research institutions in a large number of countries. Maintaining existing collaborative networks and developing new linkages is of critical importance to the CBTBR. For this reason, members continued to devote significant time and effort to networking.

New networks and linkages
The Wits node was invited to participant in a 24-member consortium of research teams from Europe, South Korea, India and South Africa, led by Prof. Stewart Cole (EPFL, Switzerland) that applied for funding for a TB drug discovery project under the EU FP7 program. If successful, this grant will commence in January 2011 and will sport activities in the Wits node for 4 years.

NAME INSTITUTION NATURE/ PURPOSE, OUTPUTS AND FUTURE DIRECTION OF COLLABORATION

Prof. John D. McKinney

École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland

Collaboration on the mechanisms of propionate catabolism, co-author on a manuscript published in 2008 and joint awardee (with Prof. Mizrahi) on a three-year grant from Swiss/ SA Joint Research Programme. Dr. Warner visited Prof. McKinney’s lab in July to discuss the collaborative research project.

Dr. Clifton E. Barry III and Dr. Helena Boshoff

Tuberculosis Research Section, Laboratory of Host Defenses, National Institute of Allergy & Infectious Diseases, NIH, Rockville, MD

Collaborating members of the “IM TB” Consortium funded through SBRI. Hosted Dr. Garth Abrahams during his 4-month working visit to the NIAID in 2009.

Prof. Gilla Kaplan

Public Health Research Institute, International Center for Public Health, Newark, NJ

Ongoing collaboration in the area of in vivo phenotyping of mutant strains of M. tuberculosis. Profs Kaplan & Mizrahi Jointly run the TB Basic Sciences component of the CU-SA Fogarty AITRP. Visited the Wits node  in October 2009

Prof. Česlovas Venclovas

Institute of Biotechnology, Vilnius, Lithuania

New collaboration on the structure and function of a novel mutagenic complex in mycobacteria. Spent a week in the Wits node  in March 2009 to further the collaboration with Dr. Warner and Ms. Ndwandwe

Prof. Heini Dirr

University of the Witwatersrand

New collaboration on the expression and structure determination of members of a novel mutagenic complex in mycobacteria

Dr. Deborah Hung

Broad Institute of Harvard and MIT, Boston, USA

Collaborating member of the “IM TB” Consortium funded through the SBRI. Also collaborating on the characterization of Rpf-deficient mutants of M. tuberculosis

Prof. Eric Rubin

Microbiology and Immunology, Harvard Medical School, USA

Collaborating member of the “IM TB” Consortium funded through SBRI. Visited the MRU in November 2009. Will co-host Ms. Ndwandwe during her Fogarty training fellowship in 2010

Prof. David Sherman

Seattle Biomedical Research Institute, USA

PI of the “IM TB” Consortium funded by the Bill & Melinda Gates Foundation

Prof. James Sacchettini and Dr. Tom Ioerger

Biochemistry and Biophysics, Texas A&M University, College Station, TX

Collaborating members of the “IM TB” Consortium funded through the SBRI. Also collaborating on whole-genome sequence analysis of strains of M. tuberculosis.

Prof. Sir Tom Blundell and Prof. Chris Abell

Cambridge University, UK

Collaborating members of the “IM TB” Consortium funded through the SBRI

Prof. Jean Content

Institut Pasteur Bruxelles, Brussels, Belgium

Collaboration on genome duplication in M. smegmatis resulted in co-authored publication in 2006

Dr. Chris Sassetti

University of Massachusetts, USA

Collaborating member of the “IM TB” Consortium funded through the SBRI

Prof. Tanya Parish

Barts and the London, UK & Infectious Diseases Research Institute (IDRI), Seattle, USA

Collaborating member of the “IM TB” Consortium funded through the SBRI

Prof. Stewart Cole

EPFL, Lausanne, Switzerland

PI of the More Medicines for Tuberculosis (MM4TB) Consortium, which has applied for funding under the EU FP7 framework

Prof. Vickery Arcus

AgResearch, University of Waikato, New Zealand

Collaboration on the role of VapBC toxin-antitoxin modules in the physiology of M. tuberculosis

Prof. Gregory Cook

University of Otago, Dunedin, New Zealand

Collaboration on the role of VapBC toxin-antitoxin modules in the physiology of M. tuberculosis

Prof. Petros Karakousis

Johns Hopkins University, Baltimore

New collaboration on nucleotide pool determination in mycobacteria. Will host Dr. Cliff Magwira in 2010 for short-term training fellowship

Dr. S. Sampson

Imperial College, UK

The evolution and function of the PE and PPE gene families (2001-present) & the ESAT-6 secretion system interactome (2007- present).

Dr. H. Mardassi, Mr. A. Karboul and Mr. A. Namouchi

Institut Pasteur, Tunisia

Characterization of M. tuberculosis lineages through the PE/PPE gene family (2002 - present)

Dr. W. Bitter and Mr A. Abdallah

Vrije Universiteit, Amsterdam, Netherlands

The trafficking of the M. tuberculosis PE and PPE proteins (2006 – present).

Dr. John Ho

Cornell University, New York, USA

Characterization of M. tuberculosis lineages through the PE/PPE gene family (2007 - present).

Prof. J. Ho, Dr. A. Gibson and Prof. R. Huard

Cornell University, New York, USA

The dissemination of the major RDRio sub-lineage of the LAM M. tuberculosis spoligotype family in Luso-American countries, Portugal and Africa

Dr. H. Mardassi

Institut Pasteur de Tunis, Tunisia 

Characterisation of LAM evolutionary history (2007-present).

Prof. A. Steyn

University of Alabama, Birmingham, USA

The ESAT-6 secretion system interactome (2007- present).

Prof. VPMG Rutten, Dr. I van Rhijn, Dr. AP Koets

Utrecht University

Non-tuberculous mycobacteria in wildlife (WOTRO Integrated program proposal) (2007).

Dr. R Anthony

KIT The Netherlands

MLPA assay for the detection of ofloxacin resistance

Prof D van Soolingen

RIVM The Netherlands

Evolution of the Beijing genotype Lineage

Dr. Kristin Kremer

RIVM The Netherlands

Whole genome sequencing of Beijing genotype strains

Dr. V Dartois

Novatis Singapore

MassArray detection of mutations conferring drug resistance

Prof. E Bottger

University of Zurich

Development and evaluation of novel genetic based diagnostics for drug resistance.

Prof. E Nardell

AIR facility, Witbank

Transmissibility of drug resistant TB

Prof. Sturm

UKZN and LifeLab

Whole genome sequencing and development of a genetic based diagnostic for second-line drug resistance

Prof. Erwin Schurr

McGill University, Montreal, Canada

Genetic epidemiology. Poster outputs;  4 papers published 2009-2010.

Prof Laurent Abel & Alexandre Alcais

INSERM / Université Paris 5, France

Analysis of genetic epidemiology. Poster outputs; 4 papers published 2009-2010.

Dr. Iris Grossman

GlaxoSmithKline, NC, USA

Genetic susceptibility to TB.

Dr. Alkes Price

Harvard School of Public Health, Boston, USA

New collaboration. Analysis of admixture mapping.

Dr. Ingileif Jonsdottir

decode, Iceland

Genetic susceptibility to TB.

Dr. Lluis Quintana-Murci

Institut Pasteur, Paris,
France

Genetic susceptibility to TB and population structure. Paper expected 2010.

Prof. Stefan Schreiber and Dr. Almut Nebel

Christian Albrechts University, Kiel, Germany

Investigation of candidate genes in TB. Resulted in 2 co-authored publications in 2007, and 2 co-authored publications in 2009

Prof .Megan Murray

Harvard / Broad institute

Various project including the evolution of XDR-TB strains; other mechanisms of drug resistance (in addition to genomic mutations); mechanisms of resistance to 2nd line drugs; strain fitness; certain strain families may have both increased fitness and increased potential for acquiring drug resistance. All of these projects involve whole-genome sequencing, proteomics, and microarray. Prof. Murray is directly involved in project planning, paper writing, funding proposals (NIH and Wellcome trust).   

Dr. Judit Nagy

Imperial College London

Proteomics of large clusters (more transmitted) vs. small clusters (less transmitted) in the same strain family after other criteria to select isolates have been taken into consideration. The aim is to identify proteins that are differentially expressed in the same strain family which may give them an advantage to transmit better.

Prof. Harald Wiker

Bergen University, Norway

Ongoing collaboration on the M. tuberculosis phosphorylome.
New collaboration on the detection of drug resistance by single run multi-locus sequencing.
New collaboration on the M. tuberculosis secretome.

Dr. Hernandez Pando Rogelio

National University of Mexico

Test different drug resistant strains (MDR / XDR) in a mouse model for strain fitness/virulence. The isolates are the same as described above and will compliment the data obtained by molecular investigations.

Dr. Cheryl McDermott

MSF

New collaboration on drug resistance in Khayelitsha, Western Cape.

Prof. Tom Alber

Berkeley

New collaboration on the M. tuberculosis lipidome.

Prof. Brigitte Gicquel

Pasteur Institute

New collaboration on mutation in M. tuberculosis DNA repair genes.

Prof. Kathy Eisenach

Arkansas, USA 

Mechanisms of strain fitness in an in vitro THP-1 cell line model. Project is in planning phase.

Prof. Stefan Kaufmann

Max Planck Institute for Infection Biology, Berlin, Germany

Collaborators on BMGF-funded project.

Prof. Henry Boom

Cleveland, Ohio, US

Collaborators on BMGF-funded project.

Prof. Hazel Dockrell

London School for Hygiene and Tropical Medicine, London, UK

Collaborators on BMGF-funded project, Co-applicants on grant application to BMGF.

Dr. Mark Doherty

Statens Serum Institute, Kopenhagen, Denmark

Collaborator on BMGF-funded project, collaborators on NIH-sponsored study

Dr. Martin Ota

MRC, The Gambia

Collaborators on BMGF-funded project.

Prof. Harriet Mayanja

Makarere University, Uganda

Collaborators on BMGF-funded project.

Prof. Ronnie Anderson & Dr. Caroline Cholo

MRC/ UP Unit on Inflammation & Immunity, University of Pretoria

Collaboration on the role of potassium transport in mode of action of anti-tubercular action of riminophenazines.

Prof N. Beyers, Dr A. Hesseling, Dr S. Tonkin, Prof B. Marais

SU

Non-tuberculous Mycobacteria (NTM) - Prevalence and Clinical relevance in HIV-infected and HIV-uninfected children (2006 - present).

Prof. N. Beyers

DTTC, SU

Ongoing collaboration of the molecular epidemiology of M. tuberculosis in the W. Cape.

Dr. A. Michel, J. Godfroid, K. Coetzer & N. Kriek

Onderstepoort Veterinary Institute

Non-tuberculous mycobacteria in wildlife (WOTRO Integrated program proposal) (2007 - present).

Prof. L. Dicks

Microbiology, SU

Bacteriocins as a possible method to treat M. tuberculosis infection (2007-present). One publication in J. Appl. Microbiol. 2007.

Prof. S. Mehtar

Unit for Infection Control, Tygerberg Hospital

The anti microbial activity of copper and copper alloys against nosocomial pathogens and M. tuberculosis isolated from healthcare facilities in the Western Cape– an in-vitro study. One publication in J. Hosp. Inf. 2008.

Prof. Kelly Chibale

Dept Chemistry
University of Cape Town

Screen antituberculosis lead compounds

Dr Thavi Govender

Dept. Chemistry, UKZN

Test antituberculosis activity of existing antituberculosis drug derivatives. K. Onajole 2009

Prof Green

Dept Chemistry, UWC

Screen new compounds and derivatives for antituberculosis activity

Dr. S. Todorov

Univ. Sao Paulo, Brazil

Antituberculosis activity of Bacteriocins (Todorov, 2008)

Dr C. Kenyon

CSIR, Pretoria

Dormancy regulators of M.tb in human macrophages.

Dr. Haynes

Hong Kong University of Technology

Testing new compounds for antituberculosis activity

Prof Peter Folb

Pharmacology, UCT

Testing derivatives of Diphenyl Oxazole for antituberculosis activity

Ms. Marlein Bosman

NHLS , Green point

Collaborator on all our projects – provides routine samples.

Dr. Sias May

TB Control program in Suidkaap/ Lawwaaikamp

TB Control strategy.

Dr. Danie Theron

Eben donges Hosp, Worcester

New project on DOTS program on farms.

Dr Else Marais

Wits/NHLS

Ongoing collaboration on the molecular epidemiology of drug resistant TB in Gauteng.

Prof C. Reinecke & Dr du Toit Loots

North West University

New collaboration on the M.tuberculosis metabolome.

Prof C Wright

NHLS Tygerberg

The diagnostic utility of FNAB

Dr. Alistair Calver

Gold Mine in Northern province

Ongoing, outbreak of drug resistance in a setting with a good control program.

Prof. Willem Hanekom

IIDMM, UCT

Sharing of technology (multicolour FACS, Luminex machine), sharing of samples, manuscript accepted for publication.

Prof. Frank Brombacher

IIDMM, UCT

Sharing of expertise (murine helminth models).

Dr A. Hesseling

SU

New collaboration to investigate genotype-immunological phenotype correlations in children.

Dr Cahal Seioghe, and team

NBN node, Cape Town

New collaboration. Analysis of whole-genome sequence data.

Mrs. Lungi Kwitshana

MRC, Durban

Collaboration in project on worm-HIV co-infection.

Prof. Keertan Dheda

Lung Institute, UCT

Collaboration in diagnostic/biomarker project.
Molecular epidemiology of XDR-TB

Dr. Anna Mandalakas

Case Western Reserve University, USA

Collaboration of diagnostic studies in paediatric TB.

Dr. Marc Jacobsen

Bernhard Nocht Insitute, Hamburg, Germany

Collaboration on helminth/TB co-infection studies.

Dr Muazzam Jacobs

University of Cape Town

New collaboration to assess the impact of steroid hormones on protective immunity to Mycobacterium tuberculosis in a mouse animal model.

Conference and Workshop Organisation

International TB conference hosted and organised by CBTBR SU node
The Stellenbosch University node held an international TB conference focusing on the Effect of Genetic Variation in Mtb on Vaccine Escape and the Acquisition of Drug Resistance, at Lanzerac wine estate between the 16th and 18th of September 2009. Twenty-four delegates from Europe, Asia, Central and South America and South Africa presented their findings on how Mycobacterium tuberculosis adapts to the selective pressure of antibiotics and vaccines. Ground breaking research was presented concerning the influence of vaccines on the virulence of M. tuberculosis, the possible role of DNA repair genes in the evolution of Mycobacterium tuberculosis, the mechanisms whereby M. tuberculosis develops mutations, extensively drug-resistant tuberculosis (XDR-TB), novel mechanisms which define the level of drug resistance and whole genome sequencing as the future tool for molecular epidemiology.  Prof Rob Warren, Prof Gey van Pittius, Prof Tommie Victor, Dr Chris McEvoy, Dr Madeleine Hanekom, Dr Elizma Streicher and Ms Kim Hoek from the SU node and Dr Digby Warner from the Wits node presented at the meeting.

TB Trials Consortium (TBTC) visit to the CBTBR SU Node
Colleagues from George Washington University, Debra Benator, Fred Gordin and Donna Conwell visited the CBTBR SU node from 24 to 27 February 2009 to work on a joint strategy for a SU application to the CDC-sponsored TB Trials Consortium (TBTC). Professor Benator the director at the Infectious Diseases Clinic at the VA, gave an overview of TBTC trial experiences gained during the past 10 years on 27th February; the lecture was well attended by a broad spectrum of clinicians and researchers.

The TBTC visit was hosted by the CBTBR and the Desmond Tutu TB Centre. This collaborative effort brings together a strong group of adult and paediatric TB and HIV researchers at the faculty in a joint consortium called TB SUN. TB SUN will aim to join larger collaborative TBTC international activities to implement trials of new TB therapies where most needed, including in children.


Networking

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