MM4TB logo
Partners

The More Medicines for Tuberculosis (MM4TB) consortium consists of 25 partners from 13 countries in Europe, America, Asia and Africa.

The École Polytechnique Fédérale de Lausanne (EPFL), has joined with two large pharma, (AstraZeneca and Sanofi-aventis), one large diagnostics company (Alere), four SMEs (Vichem, Cellworks, CDD, Tydock), twelve universities (Uppsala, Pavia, Cambridge, Queen Mary's, London, Padova, Comenius, Piemonte Orientale, the Basque Country, Zaragoza, ETH Zurich, and Cape Town), five research institutes (Institute Pasteur in Paris, Institut Pasteur of Lille, the Bach Institute of Biochemistry, the John Innes Centre and the Indian Academy of Sciences) and a professional scientific management company to develop new drugs for successful and shorter treatment of Tuberculosis (TB).


École Polytechnique Fédérale de Lausanne (EPFL)

EPFL

The École Polytechnique Fédérale de Lausanne (EPFL) is one of the world's leading Technical Universities, specialized in teaching and research in basic sciences, physical sciences and engineering. A Faculty of Life Sciences was recently created and this harbours four research institutes focusing on bioengineering, cancer, global health and neurosciences. Prof. Cole is leading the Global Health Institute (GHI), which is using a multidisciplinary approach to study infectious diseases, including tuberculosis, with particular emphasis on translational research. The GHI has state-of-the-art equipment for research in molecular and cellular microbiology and has fully equipped category 3 laboratories for microbiology, tissue culture and animal experimentation. The environment is quite exceptional in terms of the scientific and human resources, most notably the interaction between engineering, informatics and life sciences. The GHI has access to chemical libraries and its own dedicated screening platform.


Team Members

Prof. Stewart Cole, a world-authority on tuberculosis and leprosy with 25 years experience, has worked extensively in the areas of mycobacterial drug resistance, genetics, genomics, pathogenesis and, more recently drug discovery.

John McKinney is Professor of Bacteriology at the EPFL and received a Ph.D. from The Rockefeller University (1994).

The "Laboratory of Protein Engineering" (Head: Kai Johnsson) is working on the development and application of innovative research tools to study protein functions and protein-drug interactions in vivo and in vitro.

Dr Gerardo Turcatti, Director of the Biomolecular Screening Platform.
The Biomolecular Screening Facility (BSF) at the EPFL School of Life Sciences (Faculté des sciences de la vie, FSV) is a multidisciplinary laboratory created for performing high throughput screening in life sciences-related projects.


More information

Website: http://www.epfl.ch

AstraZeneca (AZI)

AZI logo

AstraZeneca is one of the world's leading pharmaceutical companies, quoted on the UK, US, and Swedish Stock Exchanges. We spend over £7 million each working day on the global research and development of innovative, effective medicines. Astra AB of Sweden and Zeneca Group of the UK officially merged on 6 April 1999 to form AstraZeneca PLC and the merger became operational on 1 June 1999.

AstraZeneca India (AZI) is fully owned subsidiary of AstraZeneca Plc. UK and is the AZ centre of excellence for the discovery of novel therapies for developing world diseases. The unit comprising of 110 researchers is entirely devoted to the discovery of novel treatments for Tuberculosis. AZI is an integral part of AZ's R and D and the programmes at Bangalore are run as part of the overall R and D strategy of AstraZeneca. AZI has at Bangalore the entire drug discovery infrastructure and over the last decade built extensive experience in drug hunting for Tuberculosis. AZI delivered it first candidate drug in late 2009. Being an integral part of global R and D platform, researchers at AZI have access and support from the > 10,000 AZ researchers across the globe. Additionally AZI can access all infrastructure and information generated across AZ R and D, one of the main platforms on which the research at Bangalore is sustained.


Team Members

Dr T.S. Bangalesh, Vice President, Discovery.

More information

Website: http://www.astrazenecaindia.com/

Uppsala University (UU)

AZI logo

Our Structural Biology Programme is part of the Department of Cell & Molecular Biology, Uppsala University. This Programme has long experience in all aspects of macromolecular crystallography, including protein expression, crystallization, methods development for model building, refinement and validation, Internet based functionality, and structure solving. Our Programme makes a major contribution to RAPID (Rational Approaches to Pathogen Inhibitor Discovery), an integrated Centre for structural biology and medicinal chemistry, which is primarily working on targets from Mycobacterium tuberculosis (with 23 papers published to-date on M. tb). The structural biology component of RAPID is a close collaboration between Prof. Mowbray (who leads crystallography and target selection), Prof. Unge (who is responsible for protein production), Mrs. Bergfors (who is responsible for crystallization) and Prof. Jones (who plays a largely administrative / crystallographic techniques-oriented role). Together, we have solved the structures of 19 unique MTB enzymes, including 33 PDB entries and 16 more in progress). The computational chemistry portion of RAPID is led by Prof. Johan Åqvist (ICMB), while medicinal chemistry is coordinated by Profs. Karlén & Larhed from the Department of Medicinal Chemistry, Uppsala University.


Team Members

Prof. Sherry L. Mowbray
Prof. Alwyn T. Jones
Prof. Anders Karlén.

More information

Website: http://www.uu.se/en/

University of Pavia (UNIPV)

University of Pavia logo

The Department of Genetics and Microbiology (DGM) was created in 1982 by merging the Institutes of Genetics (1948), Microbiology and Plant Physiology (1969) and Crystallography (1971). The research activity performed by people working at the DGM covers many scientific areas: microbial genetics, biochemical and cellular genetics, animal genetics, human genetics, evolutionary and population genetics, immunogenetics, tumor genetics, microbiology, plant physiology and biochemistry, biocristallography and molecular biology.

The Laboratory of Molecular Microbiology has a recognized experience in the study of antibiotic resistance mechanisms (especially those based on efflux pumps) and in genetics and molecular biology of mycobacteria. During the last four years the Team is dealing with target identification of new antitubercular drugs. The team has experience in mycobacterial genome sequencing, DNA libraries construction and screening, mycobacterial gene inactivation, and experience in the cloning and expression of mycobacterial recombinant proteins in Escherichia coli. The Leader, Prof. Giovanna Riccardi, has established herself as an expert in the field of mycobacteria with important contributions to understand innate drug resistance and drug target identification of new drugs. She has obtained grants from different sources (Research program FAR funded by the University of Pavia; WHO; grants from the ECV and VI Framework Programmes, Ministry of University and Research, Fondazione Fibrosi Cistica). The team will be primarily involved in the identification and characterization of potential drug targets. In particular our expertise on working with different mycobacteria as well as in drug resistance and mechanism of action at the DGM will be of central importance for the success of the project.


Team Members

Prof. Giovanna Riccardi

More information

Website: http://www.unipv.eu/on-line/en/Home.html

University of Cambridge (UCAM)

University of Cambridge logo

The Abell and Blundell groups have pioneered the use of fragment based drug discovery approaches. A significant part of their research effort is focused on using this methodology to discover new medicines for tuberculosis. The research involves using biophysical methods (led by Dr Ciulli) to identify small molecule fragments that bind to the target protein. The fragments are then located on the protein using X-ray crystallography (led by Professor Blundell and Dr Hyvonen). There then follows iterative rounds of synthetic elaboration (chemistry directed by Prof Abell) and structural biology to make increasingly potent inhibitors. The Cambridge group is presently using this approach to study 5 targets in Mycobacterium tuberculosis.


Team Members

Prof. Chris Abell

Prof. Sir Tom Blundell


More information

Website: http://www.cam.ac.uk/

Queen Mary, University of London (QMUL)

QMUL logo

Professor Tanya Parish leads the TB research Group and has 20 years experience in the mycobacterial field including extensive work with M. tuberculosis. Her group focuses on developing and using the latest genetic methods for studying the basic biology of M. tuberculosis with particular reference to novel drug targets. Recent work has focused on the mechanism of antibiotic resistance to ethambutol and fosmidomycin, development of novel inhibitors and transport into bacterial cells, as well as the identification of vulnerable metabolic pathways in M. tuberculosis. The group has access to a dedicated laboratory facility for handling M. tuberculosis as well as all the equipment required for molecular work and microscopy.


Team Members

Prof. Tanya Parish

More information

Website: http://www.smd.qmul.ac.uk/

Institut Pasteur (Pasteur)

Institut Pasteur logo

The Institut Pasteur (IP) is a world-renowned centre of excellence for its research on infectious diseases. IP offers an outstanding research environment for tuberculosis research including state of the art structural biology facilities, biosafety level 3 laboratories and animal houses, as well as excellent imaging facilities and other technical platforms.


Team Members

Prof. Pedro M. Alzari, Unité de Biochimie Structurale, Institut Pasteur, has been working in protein crystallography for the last 25 years, and has published over 150 papers in refereed journals. His team was among the first laboratories to focus on specific mycobacterial protein families, soon after the complete genome sequence of M. tuberculosis became available, and produced the first available structural information on bacterial serine threonine protein kinases.

Dr. Roland Brosch is a well known specialist in functional and evolutionary analyses of tubercle bacilli, who gained his broad experience in mycobacterial research during more than 10 years in Prof. Stewart Cole's unit, where he had important impact on groundbreaking projects like the M. tuberculosis H37Rv- or the BCG genome projects, as well as on pioneering ESX work.


More information

Website: http://www.pasteur.fr/ip/easysite/pasteur/en

Bach Institute of Biochemistry (INBI)

INBI logo

The department has very good experience in medicinal chemistry and rational drug design with special interest in developing antimicrobial and antiviral agents. Our recent work in drug development has focussed on antituberculosis drug and as result of our effort in cooperation with several European scientific groups (FP6 NM4TB; LSHP-CT-2005-018923) a new class of synthetic organic compounds having high antituberculosis activity in vivo and in vitro was discovered (1,3-benzothiazinones). One compound from this group is under in-depth preclinical investigation now. Our team makes extensive use of advanced methods of medicinal chemistry, rational drug design and study of metabolic transformations. We have good experience in "Hit-To-Lead" process that has been obtained in several successful drug development programs.


Team Members

Dr. Vadim Makarov

More information

Website: http://www.inbi.ras.ru/index-e.html

University of Padova (UNIPV)

Padova logo

The laboratory has strong experience in the genetic manipulation of M. tb and transcriptional profiling with a special interest on the role of global regulators (e.g. sigma factors) in virulence development. Riccardo Manganelli recently coordinated an FP6 STREP project entitled "Transcriptional regulation and cellular localization of mycobacterial cell cycle proteins during dormancy" and is actually part of two EU programs aimed at the characterization of novel TB secretion systems ("Novel secretion systems of Mycobacterium tuberculosis and their role in host-pathogen interaction") and the design of new technological platforms for the development of vaccines against poverty diseases ("Highly Innovative Strategies for Vaccination to Poverty Related Diseases"). In the past few years the lab has developed a repressible promoter system based on two repressors (TetR and Pip) allowing stringent repression of M. tb genes and demonstrated its suitability for the construction of conditional mutants in M. tb (Serafini et al. 2009). Based on its experience in the genetic manipulation and gene regulation in mycobacteria.


Team Members

Prof. Riccardo Manganelli

More information

Website: http://www.unipd.it/index_en.htm

Comenius University, Bratislava (UNIBA)

UNIBA logo

The main focus of research carried out in the laboratory is studying the biosynthesis of the mycobacterial cell envelope. Our goal is the establishment of the functions of the genes that have been proposed to participate in this process by in silico studies and biochemical characterization of the identified proteins. Although the group in Bratislava has been established only recently, leading personnel involved in it received training at the top institutions for mycobacterial biochemistry and genetics (Katarina Mikusova - 4 years at CSU, Fort Collins, Prof. Brennan's laboratory; Jana Kordulakova - 3 years at IP, Paris, Prof. Gicquel's and Dr. Jackson's laboratory; 4 months at CSU). The team was part of the NM4TB consortium (LSHP-CT-2005-018923) and within this collaboration it contributed to identification of the molecular target of benzothiazinones, novel perspective candidates for the development of the drugs against tuberculosis.


Team Members

Dr Katarina Mikusova

More information

Website: http://www.uniba.sk/?en

Vichem Chemie (VICHEM)

VICHEM logo

Vichem is a privately founded biotechnology company with 32 scientific employees and 7 PhD students. Vichem is highly specialised in developing kinase inhibitors since 1999. The CEO has more than 25 years experience in kinase inhibitor chemistry.

Vichem has extensive experience in drug discovery for signal transduction therapy and developed a unique knowledge-base in successful collaboration with partners like the Max Planck Institute for Biochemistry, Martinsried Germany; Genentech USA, Sugen Inc., San Francisco, USA and Axxima Pharmaceuticals AG, Munich, Germany. Vichem provides Medicinal Chemistry capabilities based on its unique, in-house developed, Nested Chemical Library™ (NCL) method. The NCL was designed on the platform of an up-to-date knowledge base which has been built up from the experiences accumulated in the recent 20 years of kinase inhibitor chemistry. The NCL library is organised around more than 110 core structures, providing a very diverse kinase inhibitor library available for drug discovery. It contains more than 12000 potential kinase inhibitor compounds including 500 published clinically relevant leads and a big series of proprietary compounds; furthermore it contains inhibitors against 124 identified kinases.

Vichem and its predecessor company, Biosignal Ltd. took a significant part in the development of two drug candidates (TT-232 and SU101) currently in Phase II. and Phase III. clinical trials, developed several preclinical lead molecules for their partners and have lead compounds and/or early preclinical candidates for tuberculosis, influenza, AIDS and other pathological kinase targets. Vichem established partnership with various European, American and Japanese institutions and companies; coordinates a European FP6 Tuberculosis project and participates in 5 European research programs. Vichem was a member of the FP6 NM4TB consortium.


Team Members

Prof. György Kéri

More information

Website: http://www.vichem.hu/

John Innes Centre (JIC)

JIC logo

The John Innes Centre is the largest institute for plant and microbial science in Europe, with major programmes in microbial genomics, natural products and antibacterials. Prof. Maxwell is a world leader on DNA topoisomerases, which are key validated targets for antibacterial agents. In particular, the lab has carried out ground-breaking work on the understanding of the molecular basis of the action of antibacterials and toxins on bacterial DNA gyrase and has made significant contributions towards the discovery of new drugs. Dr. Lawson is an expert crystallographer with a long track record on solving structures of microbial proteins. In collaboration with the Maxwell lab, they have investigated the action of gyrase-specific antibiotics. This team worked together with other European groups on the highly successful CombiGyrase consortium (EU FP6 grant: LSHB-CT-2004-503466), which successfully engineered novel aminocoumarin antibiotics. The team will now characterise M. tb gyrase as a drug target and investigate the action of inhibitors and toxins, and evaluate their potential as novel gyrase-specific antibacterial agents.


Team Members

Prof. Anthony Maxwell

More information

Website: http://www.jic.ac.uk/corporate/index.htm

Indian Institute of Science (IISC)

IISC logo

The Department of Microbiology and Cell Biology at IISc has a long tradition of working with M. tb and other mycobacteria. Professor Nagaraja's group has a long history of working with DNA transaction processes essential for cell survival. He has been working on DNA gyrase and topoisomerase I from mycobacteria for more than 20 years. These efforts have led to the development of new inhibitors of the enzyme. Recent work on topology modulation has led to identify gyrase inhibitory proteins. In parallel, they have identified consensus promoter elements, elucidated factor dependent and independent termination mechanisms. Promoter RNAP interaction studies and topology - transcription coupling are the other research interests. Thus, the expertise on the molecular biology and biochemistry (structure - function analysis, assay development, inhibitor development) of target proteins has resulted in more than 115 research publications and would be an important value addition to the consortium.

Team Members

Prof. V. Nagaraja

More information

Website: http://www.jic.ac.uk/corporate/index.htm

Cellworks (Cellworks)

Cellowrks logo

Cellworks is focused on simulating in-silico the whole cell function of the pathogen M. tb and its response to internal and external perturbations at the molecular and kinetic detail. A detailed kinetic platform for E. coli has just been completed (with experimental validation) through a collaboration between AstraZeneca India (AZ) and Cellworks (CW). In addition, the E. coli platform was used to predict the behavior of M. tb in similar metabolic areas. These were in the pathways of CoA biosynthesis and Branched Chain amino acid synthesis. In order to understand how intracellular perturbations occur due to inhibition of essential metabolic pathways, an in silico platform was built through the use of eight major E. coli pathways. The kinetics of enzymatic and pathway functioning were simulated by interconnecting a series of ordinary differential equations that describe the kinetic behavior of each enzyme in the pathway. A kinetic model is thus a computational and mathematical framework, built by using intercellular enzyme concentration and other kinetic parameters. Such a framework responds in a similar fashion to perturbations the way the natural system in question would. This type of modeling has been referred to as an "impossible" problem, primarily because of the dearth of parametric data required to give meaning to flux equations and secondly, the absence of a software that can simulate and give stable solutions to systems comprising of thousands of ordinary differential equations (ODEs). However, the proprietary Cellworks technology, iC-PHYS™, was used to create and simulate the platform. This technology has the ability to solve systems comprising of unlimited number (in thousands) of simultaneous ODEs. Thus the absence or the paucity of kinetic parameters could be overcome by numerically solving the ODEs for kinetic parameters that give stable solutions.

Team Members

Dr Santanu Datta
Dr Anand Anandkumar
Dr Ragini Singh


More information

Website: http://www.cellworksgroup.com/

University of Piemonte Orientale (UPO)

UPO logo

The research unit operates at DiSCAFF, University of Piemonte Orientale, Novara, Italy under the responsibility of Dr. Menico Rizzi, a biochemist and a protein crystallographer whose research activities have resulted in 70 publications in International journals. The group is interested in the study of bacterial enzymes involved in central metabolic pathways, NAD homeostasis amongst others. The team has skills for: high scale production of recombinant proteins in heterologous systems; purification and biochemical characterization of recombinant proteins; enzymology; crystallization and X-ray crystallography; in silico and in vitro screening as well as synthetic medicinal chemistry under the responsibility of Dr Gian Cesare Tron, a medicinal chemist of the Synthetic medicinal chemistry Unit at DiSCAFF. Our major goals are the description of the catalytic mechanism adopted by the selected target, the development of assay suitable for HTS procedures and the identification of potent and selective inhibitors. Dr Rizzi has been involved in the past in EC funded networks in the field of tuberculosis research: "New strategy for the treatment and prevention of mycobacterial diseases" (FP5; QLK2-2000-01761) and "A SME-STREP for Tuberculosis Drug Development" (FP6; LSHP-CT-2006-037237).

Team Members

Prof. Menico Rizzi
Dr Laura Canella
Dr. Silvia Garavaglia
Dr Stefano Donini


More information

Website: Institution
Laboratory


Collaborative Drug Discovery (CDD)

CDD logo

Collaborative Drug Discovery, Inc. have developed a database, which is a novel collaborative web-based platform to archive and mine a vast range of diverse objects. The database handles a broad array of data types that can be archived and kept private and secure (CDD VaultTM), selectively shared among colleagues or openly shared on the internet in standardized formats (CDD Collaborate™). The CDD platform incorporates physical chemical calculations, similarity and substructure searching, as well as Boolean search and save capabilities. CDD technologies handle heterogeneous data files from instruments and individual experiments as well as standardized csv and sdf file convertible formats. Since November 2008 and with funding from the Bill and Melinda Gates Foundation (BMGF) CDD have established a broad network of users for our database and services in the TB community (both in the US and in Europe). We have trained over 20 of these TB research groups. We have added new features to the database in response to the TB community and have consulted one-on-one with groups to use cheminformatics tools available to us to aid in suggesting putative TB targets, and to search for other compounds for testing and predict ADME/Tox properties. The team will contribute to WP2 and WP4 of this proposal. We will provide the CDD database to all collaborating groups. We will also use our software to integrate or link to the WGS data. We will be the primary contributor to the in silico target fishing process. In addition we have broad cheminformatics and computational chemistry expertise that we can apply to projects undertaken Including: pharmacophore searching, “hit-picking” (filtering, clustering and prioritizing screening hits), isostere selection, identifying SAR trends and lead optimization.

Team Members

Barry Bunin, Ph.D.
Barry A. Bunin, Ph.D. is the CEO of Collaborative Drug Discovery. Dr. Bunin received his B.A. from Columbia University and his Ph.D. from UC Berkeley.

Sylvia Ernst, Ph.D.
Sylvia Ernst, PhD is the Senior Director of Community Growth at Collaborative Drug Discovery, Inc. Dr. Ernst received her Ph.D. in Chemistry in Frankfurt.

Sean Ekins, M.Sc., Ph.D., D.Sc.
Sean Ekins is CDD's Collaborations Director with responsibility for the scientific success of collaborations. He graduated from the University of Aberdeen; receiving his M.Sc., Ph.D. and D.Sc.

Kellan Gregory
Kellan Gregory is CDD's Product Manager. He has a degree in Chemical Engineering with an emphasis in biotechnology from Tufts University.

Krishna Dole
Krishna is head of scientific informatics and has a double BA in Biology and Earth Sciences/Environmental Studies from UC Santa Cruz.

David Blondeau
David Blondeau is the Head of Software Development at Collaborative Drug Discovery, Inc. David received his M.S. in Computer Science and Mathematics from ENSEEIHT in Toulouse, France.

Anna Spektor
Anna Spektor is CDD's Head of Community Interests and obtained a Master of Science in Biomedical Engineering, and a degree in Molecular Biology from the University of Chicago.


More information

Website: https://www.collaborativedrug.com/

University of the Basque Country (UPV/EHO)

UPV EHO logo

The "Universidad del País Vasco / Euskal Herriko Unibertsitatea" (UPV/EHU) is a teaching and research institution officially founded in 1985. The university employs over 9,000 people throughout 31 faculties and schools geographically distributed in three campuses with over 50,000 undergraduate and postgraduate students. The UPV/EHU is the Spanish University offering the highest number of degrees, one third of these degrees having a quality mention from the Spanish Ministry of Education. The Unidad de Biofísica (UB) was created in 1999 as a joint center of the UPV/EHU and the Spanish Science Research Council, "Consejo Superior de Investigaciones Científicas" (CSIC - Spanish Higher Scientific Research Council, the main public research institution in Spain). The UB has two main objectives: to carry out high-quality research studies, mainly in the field of biological membranes and structural biology, and to educate young scientists according to international quality standards. The UB is equipped with state-of-the-art protein purification, protein biophysics and x-ray crystallography facilities. In addition, the UB has access to several technical facilities available at CSIC Institutes and other departments of the UPV/EHU such as gene sequencing, peptide synthesis, mass spectrometry, circular dichroism, surface plasmon resonance and atomic force microscopy. The laboratory focuses on the understanding of the biogenesis of the mycobacterial cell envelope at the molecular level. To this end we use an integrated approach including molecular biology, protein biochemistry, protein biophysics and macromolecular X-ray crystallography.

Team Members

Prof. Marcelo E. Guerin

More information

Website: http://www.ehu.es/p200-shenhm/en

Tydock Pharma Srl (TYDOCK)

Tydock logo

Tydock Pharma is a chemo-biotech company discovering new drugs targeting major infectious diseases. TydockP is a spin-off company of the University of Modena and Reggio Emilia working in the field of drug discovery research. It was founded in 2006 by Prof. Maria Paola Costi and Dr. Venturelli. M.P. Costi is a professor of the University of Modena and Reggio Emilia in the Faculty of Bioscience and Biotechnology and she is coordinating the project LIGHTS (6FP of the European Commission) on cancer, focused on Thymidylate synthase anticancer drug discovery with new mechanism of action. Dr. Venturelli is a medicinal chemist with chemistry experience in the field of drug discovery of antifolates and beta-lactamase inhibitors. They are authors of 8 patents in the area of infectious diseases and cancer. Tydock Pharma research products are mainly hit, lead and drug candidate with anti-infective activities based on an innovative mechanism of action that involves an unexplored biological target, ThyX, and Thymidylate synthase. The expert technology areas are: lead generation, target/pathway-oriented medicinal chemistry, biological activity profile and early screening (www.tydockpharma.com). Tydock Pharma has a flexible operating platform that can provide all the chemical expertises needed for candidate drug identification: library design and synthesis and selection, in parallel/combi-like chemistry, microwave chemistry, lead optimization chemistry. Tydock Pharma is currently coordinating the EUROTRANS-BIO project on Helicobacter pylori named SMART (Species specificity management in resistant infectious diseases targeting Thymidylate synthase) (http://www.eurotransbio.net/). EUROTRANS-BIO is working on the development of the European Research Area (ERA), it supports industry-driven trans-national R&D projects.

Team Members

Dr Alberto Venturelli
Prof. Maria Paola Costi
Rosaria Luciani
Dr Stefania Ferrari
Dr Marcella Rinaldi
Dr Puneet Saxena


More information

Website: http://www.tydockpharma.com/

Zaragoza University (UNIZAR)

UNIZAR logo

The group has a large experience in mycobacterial genetics, and especially in drug resistance mechanisms. The group participating in this consortium forms part of a larger Mycobacterial Research Unit at the University of Zaragoza, where other ongoing projects deal with the development of novel live vaccines against tuberculosis and molecular epidemiology of M. tuberculosis complex clinical isolates.

In recent years, the group has focused on functional characterisation of drug efflux pumps as a mechanism of drug resistance in mycobacteria. Research on this topic has been funded by national grants and also by EU funded grants in which the group has collaborated with other members of this consortium.

Our experience in characterising efflux pumps will be important for assessing whether the new drug candidates identified in other work packages of this consortium can be transported by any of the efflux pumps, hence affecting their activity. Also, influx of drug candidates into M. tuberculosis cells will be studied.


Team Members

Dr. José A. Aínsa

More information

Website: http://www.unizar.es/

Swiss Federal Institute of Technology Zurich (ETHZ)

ETHZ logo

Prof. Altmann himself has 13 years of experience in the pharmaceutical industry, many of them as a senior research leader. The core competence of the Altmann group at ETH Zürich is in the areas of natural product chemistry and medicinal chemistry. Within this framework our focus in the past has been on tubulin modulators and kinase inhibitors; a large part of this research has focused on epothilones as potent leads for anticancer drug discovery and we are one the leading groups in this area. More recently we have initiated projects on mycolactone, which is macrolide produced by M. ulcerans and is the causative agent of Buruli ulcers, and on illamycins/cyclomarins, which are cyclopeptides with potent activity against M. tuberculosis. This research is carried out in close collaboration with the Swiss Tropical Institute (Buruli, Prof. G. Pluschke) and the Novartis Institute for Tropical Diseases (NITD) in Singapore (Illamycins/cyclomarins). We are well positioned to pursue natural product-based lead optimization approaches, based on our extensive experience with the chemistry of polyketide-based macrolides such as epothilones, L-783277, peloruside A, dactylolide/zampanolide and mycolactones as well as terpenoid structures such as valerenic acid or blumiolide C. In addition, our general expertise in synthetic organic and medicinal chemistry will allow us to quickly initiate/support hit-to-lead chemistry or lead optimization for any new hits/leads that might emerge from work in the other WPs. (unpublished, ongoing work). In addition, our general expertise in synthetic organic and medicinal chemistry will allow us to quickly initiate/support hit-to-lead chemistry or lead optimization for any new hits/leads that might emerge from work in the other WPs.

Team Members

Prof. Karl-Heinz Altmann
Oliver Horlacher
Florian Glaus


More information

Website: http://www.ethz.ch/

Alere Technologies GmbH (Alere)

Alere logo

Alere Technologies GmbH is a technology company specializing in the development of miniaturized detection systems for the life sciences. The company was founded in 1998 as a venture-funded start-up with the goal to commercialize miniaturized multiplex diagnostics combining chip technology with microfluidics, microoptics and precision engineering. Since 2006 ALERE has been part of the Inverness Medical Innovations Group (IMI). Based on the long term vision of a health care provider IMI/Alere have started a preclinical development program with lead compounds from the class of the benzothiazinones to complement their diagnostics platform in the HIV/Tuberculosis field with a therapeutics approach ("Theragnostics").

Team Members

Prof. Albert Hinnen

More information

Website: http://www.alere-technologies.com

Sanofi Aventis R&D (SARD)

Sanofi logo

Sanofi Aventis R&D started TB research in 2006 and will have next year a dedicated Therapeutic R&D structure for infectious diseases. Within this organization 4 chemical series are currently under chemical optimization. 4 target-based screens have been completed for which lead selection is in progress. 2 additional targets are under validation.

In addition TB research activities are linked to Sanofi-Aventis "Access to Medicine" projects.
One of the major advanced projects is the development of a new treatment for non resistant active TB based on rifapentine.

Moreover Sanofi-Aventis R&D has a specific expertise in natural product identification, isolation and derived chemistry and proposes to screen within the context of this consortium and on phenotypic assays (non replicating, intracellular), a large collection of purified natural compounds available and that can be conditioned in various microplate formats (around 10,000 compounds). The team will also contribute the various expertise needed for lead optimization, including Cheminformatics, medicinal chemistry and ADMET.


Team Members

Dr Laurent Fraise
Dr Frédéric Galli
Dr Sophie Lagrange
Dr Veronique Leblanc


More information

Website: http://en.sanofi.com/home.asp

University of Cape Town (UCT)

Sanofi logo

Prof. Valerie Mizrahi is director of the Institute of Infectious Disease and Molecular Medicine (IIDMM) at the University of Cape Town (UCT). She and Dr. Digby Warner lead the MRC/NHLS/UCT Molecular Mycobacteriology Research Unit and UCT node of the DST/NRF Centre of Excellence for Biomedical TB Research based in the IIDMM. The research focus of their lab is on studying aspects of the physiology and metabolism of mycobacteria of relevance to drug discovery and drug resistance. This laboratory has specific expertise in mycobacterial molecular genetics which has been applied in the construction of ~150 single and multiple mutant strains of M. tuberculosis H37Rv and several hundred targeted mutants of M. smegmatis. Prof. Mizrahi has been working in TB research since 1993. She has been an International Research Scholar of the HHMI since 2000 and is a Fellow of the American Academy of Microbiology in 2009. This lab is best known for its work mechanisms of DNA metabolism, resuscitation and culturability, respiration and cofactor biosynthesis in mycobacteria. Being supported by two major grants from the South African government, research capacity development forms a major focus of this laboratory’s work. This laboratory participates in several other TB drug discovery consortia funded by grants from the Bill & Melinda Gates Foundation under the TB Drug Accelerator program (IMTB and HIT-TB), and the Technology Innovation Agency of South Africa (SATRII).

Team Members

Prof. Valerie Mizrahi

Dr. Digby Warner (Senior Scientist)

Dr. Vinayak Singh (Postdoctoral fellow)


More information

Website: http://www.uct.ac.za/

INSERM/Institut Pasteur of Lille (INSERM)

Sanofi logo
Institut Pasteur Lille logo

The Center for Infection and Immunity in Lille (CIIL)- Inserm Unit U1019- headed by Dr. Camille Locht is a newly created Institute in 2010 and contains 11 Research Units in the field of Microbiology, Immunology and Inflammation. Among them, the Unit of Molecular Mechanisms of Bacterial Pathogenesis, has been working on bacterial infections, in particular M. tuberculosis and B. pertussis, for several decades and has been participating continuously and without interruption on this EU project since the early 1990s.

The CIIL is located within the Institut Pasteur of Lille, where the Medicinal Chemistry and Drug discovery Unit, headed by Dr. Benoit Deprez has all necessary equipments for high throughput screens up and running. In addition, the Biosafety Laboratory Class 3 is certified for experiments with M. tuberculosis and will shortly be set-up with equipment for high content screening. Within the CIIL, Priscille Brodin will start a new group building on her five year experience at Institut Pasteur Korea where she had set-up and run new assays based on automated confocal fluorescence microscopy for monitoring the trafficking and growth of M. tuberculosis inside host cells, in particular macrophages.

For the last five years, Priscille Brodin developed rapid phenotypic assays based on the use of automated confocal fluorescent microscopy, coupled with dedicated quantitative image analysis, to monitor intracellular mycobacterium trafficking to phagosomes, bacterial mediated apoptosis and late growth of M. tuberculosis H37Rv in macrophages. These biologically relevant assays are amenable to high throughput screening of compounds, bacterial mutants and siRNA libraries in limited steps, can be performed within a high bio-security environment and will be adapted to the needs of MM4TB project.


Team Members

Dr Priscille Brodin

Dr. Alain Baulard


More information

Website: INSERM
Institut Pasteur of Lille