Summary
Outmanoeuvring multiple defences
Our battle against bad bacteria threatens to end in a defeat. The rise of AMR, where bacteria evolve to resist our attempts to annihilate them, means new drugs are desperately needed. While researchers have no problem coming up with new molecules that can bind to lethal bacterial targets, getting the drugs inside bacterial cells is one of the biggest stumbling blocks in antibiotic drug development. Gram-negative bacteria, uniquely troublesome bugs, are protected by two different membranes; you might find a drug that gets through one of the membranes only to find that it cannot breach the other. Once you find a molecule that can cross both membranes, these bacteria have another weapon up their sleeves in the form of efflux pumps, which literally pump the drug back out of the cell.
Tricking the bacteria with “Trojan horse” antibiotics
TRANSLOCATION discovered many features of the protective cell membranes that control the access and expulsion of compounds from bacteria. For example, several proteins contained in bacterial membranes are used by the organisms to gather food, and the research showed how bacteria might be fooled to allow entry of “Trojan Horse“ antibiotics which are designed to resemble such foods. TRANSLOCATION created new, sensitive methods to detect how much drug ends up inside the cell by means of counting molecules as they pass through single proteins. The team was able to quantify a whole range of membrane proteins at the atomic level and revealed the detailed structures of 40 different proteins involved in drug transport. They also developed new modelling approaches and a scoring function to predict permeability, which represents a loose set of “rules” about a drug’s likelihood to pass through membrane proteins.
The project partners also worked on creating a database, called the InfoCentre, that could link all the data that was generated from the different IMI AMR projects. Securing access to data and putting it together was very difficult, since every project tends to save data according to their own format and standards. This data gathering was part of another key feature of the project’s scope: learning from success and failure. It required a broad knowledge base, varying skill sets and a large body of data from multiple sources.
Legacy: a wealth of protein data, and a new company
Researchers who study molecules that can thwart the evolved protective mechanisms of bacteria will be able to use the work on proteins to help in their search for new antibiotics. The wider antibiotic research community will be able to access data from the results of all projects under the IMI AMR programme including that of TRANSLOCATION.
The experience gained from the development of the InfoCentre will contribute to IMI’s AMR Accelerator programme. Tools from the InfoCentre will form the basis of planned data and knowledge management systems to be used by multiple antibiotic discovery AMR Accelerator projects as they progress through to the clinic.
The Copenhagen-based company, GRIT42 which was founded during the TRANSLOCATION project, will help to support the day-to-day IT needs of AMR Accelerator projects and also aggregate suitable data sets. The data will be used to address complex scientific questions, such as which in-vivo models are best for testing new compounds, or how clinical trial design could be better informed by results from pre-clinical stages.
Such collaboration “impossible” in any other setting
In the area of early drug discovery, TRANSLOCATION solved a number of basic research questions from a much larger perspective compared to smaller nationwide research projects. The combination of skill sets and expertise, especially in bringing together biophysical and theoretical methods with more traditional microbiological approaches, was key to the success of TRANSLOCATION. Such close collaboration between competing pharmaceutical companies would have been impossible in any other setting. The partnership also made it easier to figure out the protocol for the collaborative relationship between the pharma companies and academic partners.
What’s next?
In order to make sure that the expertise generated by the project remains available, the project partners took advantage of the Joint Programming Initiative on Antimicrobial Resistance (JPIAMR) to set up a virtual institute. In collaboration with experts from the European Open Screen network (EU-OPENSCREEN), the platform “Translocation-transfer” is now available. It can be used as a portal for the wider scientific community to access key experimental and computational tools established in TRANSLOCATION.
Translocation-transfer will establish a working model for these networks to collaborate and share essential know-how on theoretical and experimental methods for determining compound transport. This can then be integrated into the EU-OPENSCREEN compound profiling workflow for antibiotic programmes. The knowledge transfer process will be carried out through a series of tasks and workshops and facilitated by the New Drugs for Bad Bugs (NDD4B) InfoCentre platform. In the longer term, once these methods have been adopted by EU-OPENSCREEN, the data generated from screening projects specifically related to compound transport quantification will be released via the European Chemical Biology Database and ChEMBL database. The publicly-available data can then be used by the scientific community to improve our understanding of how molecular features mediate compound transport in bacteria, benefiting antibiotic drug discovery overall.
Achievements & News
SafeSciMET trains more than 800 experts, could help create safer drugs
IMI’s SafeSciMET project established a much-needed education and training programme in drug safety sciences in Europe. In an interview with the IMI Programme Office, project coordinators Manfred Kansy of Roche and Nico Vermeulen of the Vrije Universiteit Amsterdam explain how this project will contribute to developing safer medicines in the future. ‘It is remarkable that we succeeded within the first year already to put together a curriculum for 20 courses which were harmonised with each other. In the second year we already started giving the courses,’ said Vermeulen. ‘It just amazes me that we managed to bring all these people together in one consortium, in one curriculum.’ Added Kansy: ‘What is amazing is that in the three course cycles which we had, more than 800 people have been trained. I think this is quite an achievement.’ Read the full interview
SafeSciMET regulatory course – sign up now
Registration is now open for the Regulatory Requirements and Guidelines course run by IMI education project SafeSciMET. Drug development and production underlies laws and regulations to secure protection of human, test animals and the environment. This course will provide participants with a comprehensive overview of the required in vitro and in vivo nonclinical studies, strategies for the development and risk assessment of new pharmaceuticals. While the focus of this course is mainly on the EU perspective, procedures and guidelines reflecting the international harmonisation of requirements (in the EU, US and Japanese) will also be covered. SafeSciMET offers an intense and broad training with leading experts in their field and ample opportunities for lecturer-student interactions. This course and the other single courses of the SafeSciMET programme provide new opportunities for Continuous Professional Development (CPD) and are part of European Master for Advanced Safety Sciences for Medicines degree at the University of Konstanz. The course will take place 23 to 27 January in Lisbon and the registration is open until 20 December
Sign up for SafeSciMET’s courses on clinical safety and in vitro models
Registrations are open for two SafeSciMET courses which will be held in September this year. Clinical safety: post-approval – 12-16 September 2016, Paris (France)Innovative in vitro models in drug safety assessments – 13-16 September 2016, Liverpool (UK)IMI’s SafeSciMET consortium offers a variety of custom-tailored solutions to education and training needs for drug safety specialists.
SafeSciMET Mutagenesis and Carcinogenesis Course: register now!
Registration is open for the third course on Mutagenesis and Carcinogenesis organised by IMI Education and Training project SafeSciMET. The course will be held in Vienna, Austria from 28 September to 2 October 2015 and the deadline for applications is 29 August. Besides heredity and environmental factors, chemical exposure is responsible for approximately two thirds of all cancers. The development of new chemicals holds the potential risk of mutagenic and /or carcinogenic effects on humans. Minimising these risks during drug development requires experimental approaches and expert knowledge whose basic principles will be delivered in this course.
Special emphasis will be given to the biology of cancer, the identification of mutagens and carcinogens and their modes of action on the cellular, biochemical and molecular level. In silico prediction as well as animal systems and tissue culture assays for carcinogenicity testing will be presented. Furthermore, the importance of estimating dose-dependent probabilities of mutagenic/carcinogenic effects and risk-benefit evaluation will be discussed. In case studies from industry, participants will review and assess safety data for mutagenic and carcinogenic compounds. The teachers include academia and industry experts and the interactive programme guarantees a solid understanding of the latest developments in mutagenesis and carcinogenesis.
SafeSciMET project offers new Master’s degree in Advanced Safety Sciences for Medicines
IMI Education and Training project SafeSciMET provides graduate students with a completely personalised approach to their post-graduate continuing professional development. A ‘pick and mix’ modular system of custom-tailored education and training courses in safety sciences for medicines, covering the value chain from discovery to usage, including regulatory requirements, the use of animals, and ethics provides a pan-European education and training network.
As of September this year, one of the 19 project partners, the University of Constance in Germany, can now award the Master of Science (MSc) degree in Advanced Safety Sciences for Medicines. The SafeSciMET courses and the Master’s study programme are fully compliant with the requirements of the European Bologna process for credit transfer. The University of Constance has also signed the Code of Conduct for foreign students studying at German universities, committing itself to quality standards in service and support of international students before and during their studies. In 2012, the University of Constance received the ERASMUS E-Quality Label for excellent performance in handling the ERASMUS programme and offering multiple services to incoming students.
Sign up for SafeSciMET’s next round of courses
Registration is now open for the next round of courses, starting in September 2014, offered by IMI project SafeSciMET. A good understanding of safety sciences is key for new and better medicines – from initial discovery to end use. With this in mind, SafeSciMET has developed 20 new Master-level courses in ‘safety sciences for medicines’ that are designed to meet the needs of scientists working in industry, regulatory organisations, and academia. Feedback from these courses has been extremely positive. Courses can be taken individually, or built into a well-defined study package, leading to a European Advanced Master’s Degree in Safety Sciences for Medicines, provided by the University of Constance, Germany, in close collaboration with other academic institutions providing the individual courses. For the first time, in response to student feedback, the project’s popular introductory course on safety sciences in drug discovery and development will be offered by a mix of distance or e-learning and face-to-face training.
BIOVISION and the IMI Education & Training projects
IMI and the IMI Education & Training projects will participate in BIOVISION - the World Life Sciences Forum, which will be held in Lyon, France, on March 24-26 2013. It is the place where key stakeholders can debate the impact of the latest scientific advances on society and share their vision on how to overcome health, environment and nutrition challenges. IMI Executive Director Michel Goldman will participate in the plenary session ‘How to make better use of collective intelligence’. Mike Hardman, project coordinator of EMTRAIN, will represent IMI and the IMI E&T projects in the BIOVISION Investor Conference workshop. Moreover, the IMI E&T projects are organising a satellite event on ‘Training and Education in Europe’ where they will present their activities to the forum’s participants at a booth in the exhibition area.
IMI Education & Training projects in the spotlight at DIA EuroMeeting 2013
This year’s DIA EuroMeeting, which will be held in Amsterdam, the Netherlands from 4 to 6 March, features an entire theme dedicated to IMI’s five Education & Training (E&T) projects. The sessions will feature the latest news from the projects and demonstrate how they are helping to advance education in the biomedical sector in Europe. DIA EuroMeeting visitors can also catch up with the projects and find out how IMI’s E&T projects can boost their careers at Booth 918 in the exhibition area.
Check out the IMI Education & Training projects’ video
Four of IMI’s Education & Training projects have put together a short video on their activities. In the six-minute clip, the coordinators of the EMTRAIN, SafeSciMET, Eu2P, and PharmaTrain projects present their courses and the benefits they offer for students and course providers alike. The film also features a presentation by IMI Executive Director Michel Goldman.
SafeSciMET courses – sign up now!
SafeSciMET, the IMI Education & Training program for Safety Scientists, has successfully completed its first cycle of courses in 2012, with participants giving very positive feedback. The project has now announced the start of the second course cycle, which runs from 2012 to 2014. Registration is already open for a number of courses, including Drug safety of stem cells and other novel therapeutics (26-30 November, Liverpool, UK). Topics covered in this course include the basic biology of stem cells and molecular therapies, drug safety aspects of novel therapies, the regulatory requirements for stem cells and novel therapies, and the application of stem cells in the safety assessment of conventional compounds.
SafeSciMET launches courses on clinical safety
IMI Education and Training project SafeSciMET is launching three new courses in the area of clinical safety. The course ‘Clinical safety: pre-approval’ will run on 21-25 May in Basel, Switzerland; ‘Clinical safety: post-approval’ will run on 11-15 June in Lyon, France; and ‘Stratification, pharmacogenetics and drug safety’ will run on 27-31 August in Stockholm, Sweden. Applications for the new courses are now open via the project website. Meanwhile, the deadline for applications is looming for two other SafeSciMET courses: ‘Toxicogenomics and systems toxicology’ (deadline 12 March) and ‘Pathology interpretation in drug development’ (deadline 16 March). SafeSciMET courses feature lectures by experts from both academia and industry, with case studies drawn from industry. Courses can be taken individually or combined to work towards a diploma or Master degree in safety science.
SafeSciMET courses – sign up now!
If your new year’s resolution is to boost your career by following some courses, then why not check out the courses run by IMI project SafeSciMET, the new pan-European programme on safety sciences. Applications are currently open for courses on ‘safety pharmacology’; ‘non-clinical safety assessment: strategies, ethics and protocols’; ‘biomolecular analysis: from method development to clinic’; and ‘predictive cell culture systems’, among others. SafeSciMET’s modular structure allows scientists to choose the courses that match their needs. Attending the full programme leads to an Advanced Master’s degree in Safety Sciences. Feedback from the first round of courses held in 2011 has been very positive; with students commenting: ‘The course has exceeded my expectations’, and ‘I was very pleased with the structure, the content, and the quality of the presentations and the preparedness of the presenters’.
The IMI Education & Training project SafeSciMET has opened registrations to its first course, 'Drug Discovery and Development'
This is the introductory course to the new European Masters degree for Advanced Safety Sciences for Medicines designed by SafeSciMET. The course takes place in November 2010 and consists of 5 days at the University of Copenhagen with lectures, presentations and discussions, followed by one week home assignment of case studies and course questions. Registration is open on the SafeSciMET website. A brochure on the course is available here. All the forthcoming SafeSciMET courses are listed on the website, any of them also available one by one, for instance for continuing professional development.
SafeSciMET predictive cell culture systems course – sign up now!
Registration is now open for a course on predictive cell culture systems run by IMI education project SafeSciMET. The course, led by scientists at Germany’s Martin-Luther-University Halle-Wittenberg, is a ‘blended learning’ course, meaning participants will follow a number of modules online before a three-day face-to-face session in Halle. ‘This blended course setup enables participants to prepare for the full-time F2F 3 day course next to job obligations,’ explains Sanja Dragovic from the project. ‘This means less time away from office and family.’ This course introduces the principles of cell culture systems as a tool to monitor homeostasis and early onset of functional imbalance leading to toxicity as well as their use and impact in drug discovery and development. Upon completing this course, students will be able to evaluate the strengths and the limits of specific cell culture systems and to discriminate between biochemical and cellular assays, in vitro and in vivo tests for safety purposes. SafeSciMET courses offer an intense and broad training with leading experts in their field and ample opportunities for lecturer-student interactions. The balance of academic, industry and regulatory teachers provides knowledge directly available to drug safety assessment, including dataset discussions from real case studies.
Meet the IMI Education and Training Programmes
There are five projects within IMI’s research training platform aiming to revolutionise education and training to deliver more effective and safe new medicines for patients – EMTRAIN, Eu2P, EUPATI, PharmaTrain, and SafeSciMET. Collaboration is the key to success and equally important is the projects' ability to reach intended audiences with information to raise awareness and encourage people to get involved in project activities.
Over the next six months these projects will be represented at a variety of European and international conferences through display booths, dedicated sessions or individual presentations. If you are planning to attend any of the following events, please take the opportunity to stop by and find out what is happening in the IMI training and education programmes and how you can benefit, either from a professional or personal perspective.
- DIA EuroMeeting 2014 (Vienna, 25-27 March)
- EUPATI Regional Meeting 2014 (Warsaw, 2-3 April)
- World Research and Innovation Congress (Amsterdam, 5-6 June)
- Euroscience Open Forum (Copenhagen, 21-26 June)
(December 2013)
SafeSciMET opens it's new 'safety programme
New safety programme on safety sciences' which includes courses on ‘safety pharmacology’; ‘non-clinical safety assessment: strategies, ethics and protocols’; ‘biomolecular analysis: from method development to clinic’; and ‘predictive cell culture'.
(December 2011)
Participants
Show participants on mapEFPIA companies
- Astrazeneca AB, Sodertaelje, Sweden
- Basilea Pharmaceutica International AG, Basel, Switzerland
- Glaxosmithkline Research & Development Limited, London, United Kingdom
- Janssen Pharmaceutica Nv, Beerse, Belgium
- Sanofi-Aventis Recherche & Developpement, Gentilly, France
Universities, research organisations, public bodies, non-profit groups
- Assistance Publique Hopitaux De Paris, Paris, France
- Centre National De La Recherche Scientifique Cnrs, Paris, France
- Constructor University Bremen Ggmbh, Bremen, Germany
- Fraunhofer-Gesellschaft zur Förderung der angewandten Forschung e.V., Munchen, Germany
- Fundacion Privada Instituto De Salud Global Barcelona, Barcelona, Spain
- Johann Wolfgang Goethe-Universitaet Frankfurt Am Main, Frankfurt am Main, Germany
- Synchrotron Soleil Societe Civile, Saint Aubin, France
- The University Court Of The University Of St Andrews, St Andrews, United Kingdom
- Universita Degli Studi Di Cagliari, Cagliari, Italy
- Universitaetsklinikum Freiburg, Freiburg, Germany
- Universitat Basel, Basel, Switzerland
- Universite D'Aix Marseille, Marseille, France
- Universite De Geneve, Geneve, Switzerland
- University College Dublin, National University Of Ireland, Dublin, Dublin, Ireland
- University Of Newcastle Upon Tyne, Newcastle upon Tyne, United Kingdom
Small and medium-sized enterprises (SMEs)
- Ionovation GmbH, Osnabrück, Germany
- Nanion Technologies GMBH, Munchen, Germany
- The Hyve BV, Utrecht, Netherlands
- Yelen, Ensues La Redonne, France
- grit42, Valby, Denmark
Non EFPIA companies
- Bruker Daltonik GMBH, Bremen, Germany
| Participants | |
|---|---|
| Name | EU funding in € |
| Assistance Publique Hopitaux De Paris | 103 931 |
| Centre National De La Recherche Scientifique Cnrs | 540 600 |
| Constructor University Bremen Ggmbh | 4 178 960 |
| European Screeningport GMBH (left the project) | 232 618 |
| Fraunhofer-Gesellschaft zur Förderung der angewandten Forschung e.V. | 672 679 |
| Fundacion Privada Instituto De Salud Global Barcelona | 203 639 |
| grit42 | 349 875 |
| Ionovation GmbH | 450 400 |
| Johann Wolfgang Goethe-Universitaet Frankfurt Am Main | 499 000 |
| Nanion Technologies GMBH | 293 200 |
| Nanospot GmbH (left the project) | 57 284 |
| Synchrotron Soleil Societe Civile | 304 000 |
| The Hyve BV | 326 064 |
| The University Court Of The University Of St Andrews | 886 152 |
| Universita Degli Studi Di Cagliari | 1 678 960 |
| Universitaetsklinikum Freiburg | 299 351 |
| Universitat Basel | 1 221 131 |
| Universite D'Aix Marseille | 1 653 621 |
| Universite De Geneve | 937 537 |
| University College Dublin, National University Of Ireland, Dublin | 90 313 |
| University Of Newcastle Upon Tyne | 894 625 |
| Yelen | 110 263 |
| Total Cost | 15 984 203 |
Robert Stavenger
Glaxosmithkline Research And Development LTD
United States
Mathias Winterhalter
Jacobs University gGmbH