The composition of the PreDiCT-TB consortium reflects the comprehensiveness of it’s scientific strategy, balancing integration and innovation.The twenty one partners support work in seven distinct areas or workpackages, each critical to the overall success of the project.
WP1 In vitro models
The aim of WP1 is to assemble a suite of in vitro and ex vivo assays that represent drug activity
against multiple states of MTB. The scientific focus of WP1 is on identifying those assays most relevant to
the putative persister phenotype. In addition, WP1 prioritises methods that can identify heterogeneity
amongst populations of mycobacteria and particularly those that can quantify organisms that are not
recovered using standard bacteriological techniques. Lastly, the effect of immunity will be explored using
phagocyte co-culture systems. Several systems will be adapted to more dynamic patterns of drug exposure
and experiments conducted in such a way that more comprehensive exposure-response surfaces for
combinations can be derived.
WP2 In vivo models
WP2 supports a capability to work with almost all the available animal models for tuberculosis. The
overall goal within this WP is to develop a more diversified strategy for animal work involving screening in more tractable species and benchmarking in those species exhibiting human-like pathology. Replication will enable comparison of data within as well as across species. However, the range of particularly mouse
models supported will also enable some examination of the sources of variability within individual species.
WP3 Enabling technologies
WP3 will aim to provide an array of innovative enhancements to the model systems in WP1 and 2.
Foremost among these will be single cell fluorescent imaging techniques, novel bacteriological methods for
recovery or detection of persister organisms, advanced quantitative molecular techniques and non-invasive
functional in vivo imaging techniques for animal models. Innovative techniques and biomarkers from this
WP will be applied to the assay panel in phase two of the project to evaluate their added value in modelling
WP4 Clinical Trials
In order to calibrate the integrated modelling framework which is so crucial to the success of
PreDiCT-TB, WP4 will collate and create for the first time an extensive and systematic database of
available clinical trial data in tuberculosis. Where available individual patient data will be assembled and used to validate the predictions of the preclinical systems. In addition, valuable information about the relationship between early and definitive clinical endpoints will be gained and can be directly compared to results in animals. WP4 will also facilitate the extension of existing data standards in TB
WP5 Modelling & Simulation
WP5 will comprise the most extensive mathematical modelling and simulation effort in the field of
TB to date. This WP will be the keystone of PreDiCT-TB, integrating and representing the experimental
data from WPs 1&2 and comparing it as directly as possible with the clinical data from WP4. The modular
construction of PK-PD and disease models will result in an integrated modelling framework which can be
used directly for meaningful clinical trial simulation and design, at the same time explicitly making use of preclinical and clinical information.
WP6 Project Management
Management of PreDiCT-TB will be carried out by WP6. Since the project plan is complex and
dynamic with interactions between multiple partners, the key priorities will be to facilitate the necessary
interactions between the other WPs and to maintain the overall scientific direction over the life of the
WP7 Data management
Data flow between experimentalists and modellers will be a critical success factor for the entire
project. The data needs of the different partners are diverse and need to be centrally co-ordinated. WP7 will develop data standards and formats within the TranSMART database system which has been developed for
translational projects such as PreDiCT-TB.