Report

Teaser, summary, work performed and final results

Periodic Reporting for period 1 - MIMIC (Mimicking organs on chips for high throughput drug screening and basic research)

Teaser

Development of novel drugs is a costly and time-consuming process. Often years of investments are lost as it turns out that the drug candidate is toxic to humans or does not have the effects observed previously in simple cell culture test in patients. Drug candidates are...

Summary

Development of novel drugs is a costly and time-consuming process. Often years of investments are lost as it turns out that the drug candidate is toxic to humans or does not have the effects observed previously in simple cell culture test in patients. Drug candidates are usually also tested in animals, however given species differences the behaviour of a drug candidate in animals is not always a good predictor for its behaviour in humans. Animal testing bears also several ethical issues as it might heavily impact on animal welfare. Thus there is a high demand in the pharmaceutical industry to have more reliable early test systems.
Organ on chip technology is a recent research & development area aiming at mimicking organ functionality in microfluidic systems. This technology allows the modelling of certain tissue/organ features using spatially defined culturing of cells usually under flow mimicking for example blood flow or air flow (for example in a lung on chip). In particular, organ on chips are ideally suited to establish the spatially defined co-culturing of different cell types, which increase the complexity significantly compared to standard 2D or 3D cell cultures. Thus organ on chip technology might be able to close the currently existing gap for more reliable test models for the pharmaceutical industry.
The ITN-MIMIC represents an international research consortium between academic partners and industry with a joint interest to further develop organ on chip technology and to exploit this technology for efficient drug development and basic research. The consortium is dedicated to the training of four early stage researchers in organ on chip technology. All fellows will spend at least 50% of their time with industry performing application driven research.
MIMIC focuses in particular in the further developments of two organ on chip models, which is a kidney on chip model and a gut on chip model. Aim of MIMIC is to develop models for these organs, which are suitable for high-content drug screening. Furthermore, using state of the art genetic engineering tools (CRISPR), MIMIC aims to develop specific disease models for the kidney and gut, by genetically engineering cell lines harbouring patient mutations known to cause disease. These models will be used to investigate disease mechanism in more detail but also to identify potential drug candidates and drug targets to treat the disease.

Work performed

MIMIC started with its kick-off meeting in Leiden, Netherlands where the partners came together to discuss the recruitment strategy and other organisational matters. The coordinator gave also presentations based on the coordinator presentations held in Brussels to all principal investigators involved, to ensure their proper information. The presentations were also made available to all PIs. In month 10 the recruitment of four early stage researchers was completed. The first training event for the fellows was a fellow-own meeting organised by the fellows themselves. This meeting took place in Sheffield/York, UK. The fellows gave presentations about their projects and prepared also posters, accordingly. Furthermore, the fellows invited two external speakers. During that meeting the MIMIC logo, Facebook and Twitter account were established. The first annual meeting of MIMIC was held in Leiden, Netherlands, where fellows reported on their individual project progress and further collaborations between partners were outlined. During the reporting period all fellows have performed several outreach activities, for example all fellows joined the “Discovery night” at the University of Sheffield educating the general public about their projects and organ on chip technology in particular. MIMIC fellows have also attended a workshop I: ‘Bioethics and Advanced Communication skills’ and performed two experimental training stations to acquire expertise in certain techniques provided by the consortium. All projects are still at an early stage; however cell lines, which can act as cellular disease models have been generated using modern CRISPR-technology and PDMS based kidney- and gut on chips have been manufactured. A gut on chip model suitable for high-content screening has been published already.

Final results

Currently, MIMIC has contributed to one publication in a high impact journal. The content of this publication describes the first gut on chip model established on OrganoPlates suitable for high-throughput drug screening. This publication might have a major impact on drug screening strategies of pharmaceutical companies, who might apply the published organ on chip model in their drug development programs. MIMIC will further optimize the current model and will increase its complexity. It will also exploit it to establish certain disease models on organ on chips. So far fellows have worked between 15 and 18 months on their projects and most results are expected within the second reporting period.
During the reporting period fellows have performed several outreach activities engaging with the general public. During these events the fellows have presented their research projects but have also explained the principles of organ on chip technology. In particular the point was stressed that organ on chip technology bears the potential to at least partially replace animal experiments demonstrating how research can help to tackle also controversial discussed issues in society (use of animals for research).