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BIOPOL Report Summary

Project ID: 641639
Funded under: H2020-EU.1.3.1.

Periodic Reporting for period 1 - BIOPOL (Biochemical and mechanochemical mechanisms in polarized cells)

Reporting period: 2015-01-01 to 2016-12-31

Summary of the context and overall objectives of the project

BIOPOL is an international training and research network comprising nine participants from seven countries across Europe. Participants are universities, academic institutes as well as companies. Furthermore, several academic and non-academic partners are adding further expertise to the consortium. BIOPOL is a cross-disciplinary network at the intersection of molecular cell biology, physics and engineering. Research projects are designed in a highly interdisciplinary manner requiring often the combined expertise of several consortium members.
BIOPOL is dedicated to the training of early stage researchers in the area of modern mechanobiology. Currently, it is still an open question how the physical environment is regulating cellular behaviour, moreover it is also largely unclear how the physical properties of cells contribute to cellular events like migration or tissue formation. For a long time the focus in molecular cell biology was preferentially on establishing protein/protein or protein/lipid interaction networks and signalling cascades, however it became clear that chemical signalling in the classical sense is insufficient to describe and mechanistically explain phenomena like tissue formation and cell differentiation and that the specific physical nature of the cellular environment as well as the intrinsic cellular physical properties have to be taken into account. Although there is a long tradition in life science of describing cell biological phenomena also in physical terms only recently a number of techniques have been developed allowing another dimension of investigating cell biological problems in this context at the molecular level.
A motor for undertaking research in cell biology is the establishment of knowledge allowing to understand diseases at the molecular level and to develop strategies to tackle them. A rational approach to treat human diseases is incomplete without including mechanobiological aspects. There is already very good evidence that the physical environment plays a crucial role in regulation of cellular differentiation or in regulating metastasis in cancer. Thus it is crucial that we establish a clear understanding of the mechanical cues governing cellular behaviour to exploit this knowledge for novel strategies of disease treatment, diagnostics, and tissue engineering in the future.
BIOPOL aims to understand how mechanical cues are recognised by the cell and how these signals are translated into biochemical signalling and vice versa. BIOPOL aims in particular to elucidate the role of the plasma membrane, the lipid membrane, which surrounds each cell, in sensing the environment. The plasma membrane also plays an important role in regulating selective uptake of cargo via a mechanism called endocytosis. BIOPOL investigates how the physical properties of the plasma membrane influences endocytosis. Furthermore, BIOPOL analyses the role of mechanochemical signalling in establishing and maintaining cellular asymmetries and how this is translated into tissue formation in vivo. Model systems applied here are the fruit fly Drosophila melanogaster and the worm Caenorabditis elegans. Finally, BIOPOL analyses the role of mechanotransduction in human disease. This includes in particular its role in breast cancer progression, and the role of mechanical cues in controlling/regulating the immune system.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

A BIOPOL website and twitter account has been installed and BIOPOL positions have been advertised at an early time point of the project. The BIOPOL kick-off meeting took place in Sheffield, UK. Scientific and organisational matters were discussed and the BIOPOL recruitment strategy was refined. BIOPOL has successfully hired fifteen early stage researchers (ESRs). These fifteen early stage researchers are enrolled into local PhD programs and each ESR is working on a particular clearly defined research project. Each fellow has prepared a 5-minute video about her/his research project. After all fellows had been hired a fellow own meeting was organised by the fellows themselves with the support of the BIOPOL management in Rome, Italy. This meeting allowed the fellows to meet for the first time and to introduce each other’s research project. In addition, three external speakers were invited by the fellows and gave presentations about their research, which were all within the remit of BIOPOL. Furthermore, twitter rules were established and a BIOPOL logo was designed.
The first annual meeting of BIOPOL was held in Barcelona, Spain and was organised together with the Spanish network of excellence in mechanobiology. BIOPOL principal investigators and fellows gave scientific presentations. The first annual meeting was combined with a first workshop on scientific communications for the BIOPOL fellows. BIOPOL fellows have performed numerous outreach activities including participation at science fairs and local open days.
At the end of the reporting period most of the fellows have been working on their research project between 12 and 15 months. During this time the fellows have established themselves in the respective laboratories and have performed at least one secondment to a laboratory of another consortium member. These secondments where chosen to be largely synergistic with the required expertise for the fellows research project. Furthermore, within this brief period of time already two peer-reviewed research publications have been submitted (and are now published) with BIOPOL fellows’ participation representing progress in the areas of cell volume measurement as well as microfluidic based cell culture systems.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

Most fellows worked on their research project so far for 12-15 months. Currently, we have two research publications with BIOPOL participation representing progress beyond the state of the art in the field of cell volume measurement and microfluidic based 3D cell culture systems.
The novel method to measure cell volumes allows the measurement of the volume of single cells. Cell volume is a physical property of cells so far not well investigated. The reason for this is that it is usually difficult to measure. The published technique provides the scientific community now with a novel technique to include cell volume measurements in a number of different experimental setups. As a number of diseases are accompanied by changes in cell volume this is an important aspect to be included in investigations. The second publication with BIOPOL participation developed a novel 3D cell culture system, which can be exploited for drug screening and thus could impact on the development and identification of novel drugs in terms of time and costs.
Furthermore, BIOPOL has promising first results regarding mechanisms of mechanosensing and mechanotransduction, but the preliminary nature of these results at this stage of the BIOPOL project does not allow yet to comment on their impact.
In addition, BIOPOL fellows have also participated in over twenty outreach activities aiming mostly at the general public emphasising the importance of research and the topic of BIOPOL in particular. The direct and personal engagement with the general public will impact on the general acceptance of basic and translational research as important drivers for progress in the areas of health and economy.

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