Our love is a little more painful today Nicki but we will continue to be inspired by your spirit and vision in times to come. Tonight let's first close our eyes and talk with you as we enter the early hours and your dancing begins. Let the cats of the world gather around in the deep of the night with us and see again that yes there is a planet still alive and not yet quite amused to death.
All my Love Barry
While presenting for the first time on the initial results of our "Scientists Against Malaria" drug design initiative at the Bio-IT conference in Boston this week, I used a few slides from our trip to the Caprivi Delta, Namibia to draw attention to the realities and important issues on the ground of the children needing solutions in such regions.
While on a start-up conservation field trip in a remote region of Namibia, we visited many local villages: you can consider the children here as an introduction to your ‘future patients’ for malaria treatment. Malaria is a common infection in this region which has many wetlands and a strong wet season.
Families and village communities form a critical part of the social fabric in this region. Unfortunately a high HIV infection rate is having devastating impact on such communities. Infections go untreated and many children lose their parents.
We visited a local school where we had lively interactions with the children who demonstrated their talents with enthusiasm and energy. Education requires healthy families and children so that children can attend such schooling for sufficiently long periods of time to develop stronger educational foundations to navigate the issues of this coming century for their community.
This next generation of the community is however growing up with the challenges of malaria and little medical care.
A family we interviewed with proudly showed us their material possessions. The current cost of our anti-malarials for just two weeks would exceed their entire annual income.
We can work on biodiversity conservation (e.g., recent rhino rescue work in Thanda shown). But we need a healthy, educated community involvement for it to be sustainable. Criminal groups who exploit these communities and regions for poaching must be resisted through capacity building. In collaboration together in areas of health, education and business we can build a more promising future for both the people and their rich and valuable biodiverse environment.
Consider the following realities and joining us in our collaborative work to invent new ones!
Last year we formed the “Scientists Against Malaria” (SAM) collaboration to apply modern drug design and modelling techniques in combination with industry standard infrastructure and interdisciplinary science to help develop new treatments against Malaria. The group’s first project assembles a number of leading academic researchers together with smaller innovative companies who are collaborating to develop novel inhibitors active against the Plasmodium parasite.
This is our first step in creating a collaboration learning machine for our community to enable and accelerate knowledge flow to progress the scientific research needed to develop new treatments against neglected diseases, which include other parasitic and tropical diseases, and diseases such as ALS which devastate people's health and are currently without any available treatment solutions.
Our drug design project involve situations when a number of partners collaborate to jointly solve molecular design problems as an early stage step in a drug discovery situation. The partners may involve commercial organisations, academic labs, and individual consultants who form a Virtual Organisation (VO) to collaborate on running the project, that typically has been historically carried out at a pharmaceutical organisation. The knowledge and experience of the partners involved is a critical resource and success factor for the project as is the ability to collaborate effectively. Additional resources include computer software and machinery for molecular design, modelling and virtual screening, experimental lab facilities for running assays and experiments on predicted hits for the problem studied, and supporting Information and Communications Technology (ICT) infrastructure. A significant amount of activity involving analysis, interpretation of results, synthesis and discussion is involved in many steps of the research process.
Computer-based models of Protein targets, Protein-Ligand and Protein-Protein interactions are built based on existing knowledge from crystal structures, physical chemistry and applications of bioinformatics and cheminformatics methods. A variety of methods including virtual screening, docking, pharmacophore-based design and free energy simulation methods are applied to the design of drug candidate molecules and their affinity for the target based on interactions such as involving specific hydrogen bonding and hydrophobic interactions with the active site of an enzyme. Holistic approaches to design also take into account specificity, cross-target interactions, Lipinski’s rule of 5 on druglikedness, ADME and toxicity properties of candidate molecules. Predictions are tested in the laboratory using a variety of experimental screening methods. High Throughput Screening (HTS) can be used to examine the activities of libraries of molecules against a target, whereas High Content Assays may probe a specific toxicity mechanism and property of a molecule.
A Lessons Learned process is run at the end of every significant process in the collaborative research workflow and prioritised lessons are documented into the VO knowledge base. Best Practices are agreed and documented at the start of the project. If best or better practices are discovered during the Lessons Learned process (e.g., on discussing “what went well”), they are documented into the VO knowledge base for future reference.
A complex event-driven engine is used to track all significant events occuring during the collaborative work and to provide recommendations with regards to traffic light situations (e.g., green: positive, red: negative, yellow: uncertain) where yellow situations may trigger discussion and further actions. The combination of people and infrastructure may evolve and improve as activity expands, thus becoming a Collaboration Learning Machine for Drug Discovery and Neglected Diseases Research.
I will discuss the activities of the Scientists Against Malaria (SAM) consortium at the BIO-IT conference in Boston, taking place 12 – 14 April 2011 in its collaborative drug discovery session (http://www.bio-itworldexpo.com/Bio-It_Expo_Content.aspx?id=101305). SAM was formed in 2010 from the InnovationWell Neglected Diseases Collaboration Pool as a virtual drug discovery organization to collaborate on the design of kinase inhibitors against the Plasmodium Malarial parasite. Work activities have included target selection and modelling, protein expression and assay development, computational drug design, and screening. Supported by developments on the EU FP7 funded SYNERGY and OpenTox projects, a combination of interoperable information systems, ontologies and web services were designed and deployed to manage the data, documents, computational and assay results, activity and toxicology predictions, as well as dashboards to track project progress and to support decision making. We will discuss our results, experiences and lessons learned to date, and future directions and opportunities for collaborative drug design based on our virtual organization approach.
The ToxBank project was launched in January 2011. ToxBank establishes a dedicated web-based warehouse for toxicity data management and modelling, a "gold standards" compound database and repository of selected test compounds, and a reference resource for cells, cell lines and tissues of relevance for in vitro systemic toxicity research carried out across the FP7 HEALTH.2010.4.2.9 Alternative Testing Strategies SEURAT-1 program. The project develops infrastructure and service functions to create a sustainable predictive toxicology support resource going beyond the lifetime of the program.
ToxBank should provide a unique opportunity to create an interoperable linked resource infrastructure supporting many diverse scientific research activities in the development of alternative testing methods whose ultimate goal is to replace animal testing. Developments on OpenTox should provide a strong foundation on interfaces, components, standards, and ontology that will enable and accelerate development of a modern infrastructure servicing the needs of many researchers including cell biologists, assay developers, omics technology developers, device engineers, molecular biologists, chemists, computational scientists and systems biologists.
The Seurat-1 research cluster that ToxBank is supporting had its Kick-Off meeting activities 1-3 March 2011 in Cascais, Portugal. Seurat-1 is a public-private partnership inititative between the EU's FP7 program and Colipa. The cluster involves seven projects: SCR&TOX, HeMiBio, Detective, COSMOS, NOTOX, ToxBank (infrastructure) and COACH (coordination).
This project will be jointly funded by COLIPA and the EC. Any opinions expressed in this post are those of the author. COLIPA is not liable for any use that may be made of the information contained therein
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