This past 2019 has been a great success concerning the outreach activities carried out within the Mechano·Control project. More than 320 people attended talks, workshops, discussions… related to mechanobiology.
Model on how transmembrane proteins work during a workshop at IBEC
Each year IBEC organises several workshops on mechanobiology where students explore how cells exert forces and they measure them and also create a cell membrane model. This year three schools with 25 students each have participated in this programme. Also, once a year 24 students that participate in a larger programme called “Crazy about bioengineering” come to Pere Roca-Cusachs and Trepat’s lab to do hands-on sessions on how cells perceive the surrounding environment, mechanobiology and biochemical responses.
King’s College
London participated at the 2019 Pint of Science with a talk on how forces are
key to unveiling how life functions with an audience of more than 50 people
from different ages and backgrounds.
UMCU organised
three presentations throughout the year addressed to patients and general
public about their research line on breast cancer, where more than 130 attended
the meetings.
Last but not least, INM also organised two experimental activities at their laboratories reaching 40 students and also mentoring lab practice to 5 secondary school students.
Pere Roca-Cusachs, coordinator of the Mechano·Control project and PI at the Institute for Bioengineering of Catalonia has been interviewed for the European Comission Digital Single Market news section.
Through the interview by Giordano Zambelli, Pere unfolds the aim of the project and it’s impact to society and also explains his experience working with FET.
Finding effective solutions to fight cancer is undoubtedly one of the main scientific challenges worldwide, whose success needs necessarily to build on innovative pathways of research. Mechano-Control aims to understand the physical forces that determine the spread of a wide range of diseases, with potentially vast impact on the development of new therapies.
The Mechano·Control project has launched a series of videos describing the aim of the project. In order to reach a broad audience and bring the reaserch closer to society and making it understandable, the first video explains through cartoons, the aim of the project and the research that is being carried out by the consortium members. The second video, shows the researchers behind the project. Mechano·Control is focused on the mechanical control of the biological function with the aim abrogate breast tumour progression.
Opening of the Mechanobiology of Cancer Summer School 2019
More than 60 people attended the “Mechanobiology of Cancer Summer School 2019” organised by the Mechano·Control consortium. The summer school was held in Prullans, a tiny village located at the Catalan Pyrenees between 17 and 21 of September. The event was a great success both in participation and scientific level. The aim of the summer school was to provide training on mechanobiology, and specifically its application to breast cancer, and promote interactions between professionals of the field. The school included lectures as well as practical workshops in different techniques and disciplines, ranging from modelling to biomechanics to cancer biology.
Christina Scheel during her keynote presentation
The morning sessions where dedicated to the keynote sessions from leading researchers in the mechanobiology field. The sessions left room to exchange opinions and doubts between the participants and the speakers. On the first day, Guillaume Salbreux (Francis Crick Institute) gave a lecture on “Physics of epithelial deformations” and Buzz Baum (Francis Crick Institute) on “Cancer cell division”. The second day started with Marija Plodinec’s (University Hospital Basel) keynote on “Nanomechanical profiling of living epithelial tissues in health and disease and potential applications in routine clinical setting” followed by Peter Friedl’s (St. Radboud University Nijmegen Medical Centre) intervention on Plasticity of adhesion and matrix guidance in cancer invasion and metastasis”. The last day started with Andrew Ewald (Johns Hopkins University School of Medicine for Cell Dynamics) and his talk on “Novel roles of cell adhesion in breast cancer metastasis” and to finish with the scientific sessions, Christina Scheel (St. Josef Hospital, Ruhr-University Bochum) with her lecture “Dynamic collagen deformation drives branching morphogenesis in mammary organoids derived from human breast tissue“.
The keynote sessions were followed by short talks from the attendees of the summer school, which created a space for sharing knowledge and exchanging the different research that is being carried out in different institutions around the world.
Marino Arroyo during his workshop
The afternoon sessions where more interactive and hands-on sessions with six different workshops organised by the Mechano·Control members. Marino Arroyo (Universitat Politècnica de Catalunya) gave an interactive workshop on “Vertex modelling in biomechanics” using the Matlab programme, Sergi Garcia-Manyes (King’s College London) on “Single molecule mechanics”, Manuel Gómez from Xavi Trepat’s lab (Institute for Bioengineering of Catalonia) on “Traction force microscopy”, Menno de Jong and Onno van den Boomen (Noviocell) on “Gel mechanics”, Patrick Derksen (University Medical Center Utrecht) on “Fundamentals of breast cancer biology” and Julieta Páez and Gulistan Kocer (Leibniz Institute for New Materials) on the “Chemistry of tuneable gels”.
Poster session
Finally, the last day there was a poster session, where amongst the 30 posters, the keynote speakers had to give an award to the best poster. Adam Ouzeri, PhD at LaCaN – Cell and tissue mechanobiology, from Universitat Politècnica de Catalunya (UPC) won the prize for his poster “Upscaling active gel models of the actin cortex to epithelial mechanics”.
“Wet lab scientists get wet outside the bench” Group photo
Not everything would be training, there was also time for leisure and social activities to promote networking between the participants, PI’s and keynote speakers. There was a hiking trip and a visit to the green house located near the hotel.
The ability to control key forces that drive biological functioning would be a boon for a number of medical fields. With a focus on breast cancer, an EU-funded project is bringing together different research communities to work towards understanding and controlling cellular mechanics.
Mechanical forces are created inside the body through the action of specific molecular bonds. Being able to control these would enable a giant leap forward in fields such as oncology, regenerative medicine and biomaterial design.
Tapping the potential of cellular mechanics requires the development and integration of a number of disparate technologies. The EU-funded MECHANO-CONTROL project is addressing this challenge, assembling an interdisciplinary team to design and carry out pertinent research. The scientists involved are specifically targeting new ways to impair or abrogate breast tumour progression.
The project’s ultimate aim is to understand and learn to control the full range of cellular mechanics. To do so, scientists need to find new ways to measure and manipulate complex cellular processes – from the nanometre to the metre scale.
At all stages, the MECHANO-CONTROL team is integrating experimental data with multi-scale computational modelling. With this approach, the aim is to develop specific therapeutic approaches beyond the current paradigm in breast cancer treatment.
Going further, the general principles delineated by MECHANO-CONTROL could also have high applicability in other areas of oncology, as well as regenerative medicine and biomaterials. This has the potential to bring new treatments and relief from suffering for many.
Taking it scale by scale
Working at the nanometric, molecular level, MECHANO-CONTROL researchers are developing cellular microenvironments, enabled by substances that mimic naturally occurring cell components.
On the cell-to-organ scale, the team is combining controlled microenvironments and interfering strategies with the development of techniques to measure and control mechanical forces and adhesion in cells and tissues, and to evaluate their biological response.
At the organism scale, researchers are establishing how cellular mechanics can be controlled.
A research team led by the IBEC, in collaboration with the CMR [B], discovers a mechanism that generates binucleated cells.This mechanism has been identified during the regeneration of the heart of the zebrafish, and could be associated with the extraordinary regenerative power of this animal.
Cells of the epicardium of the zebrafish with two nuclei (in blue)
After an acute heart lesion, such as a myocardial infarction, the human heart is unable to regenerate. The adult cardiac cells cannot grow and divide to replace the damaged ones, and the lesion becomes irreversible. But this does not happen in all animals. A freshwater fish native to Southeast Asia, known as a zebrafish, can completely regenerate its heart even after 20% ventricular amputation.
This extraordinary regenerative capacity has attracted the attention of
researchers from all over the world, who see the range of possibilities that
would be opened up if this mechanism of cell regeneration could be applied in
human therapies.
In an article
published today in the Nature Materials journal, a team of researchers from the
Institute of Bioengineering of Catalonia (IBEC) led by Xavier Trepat, in
collaboration with the Centre for Regenerative Medicine in Barcelona (CMR [B]),
have discovered a surprising mechanism by which zebrafish heart cells move and
divide during regeneration.
Researchers have
focused on the epicardium, which is the layer of cells on the outer surface of
the heart. Although the epicardium cells represent only a small fraction
of the heart’s mass, they play a fundamental role in its regeneration. “The
epicardium is the origin of several of the heart’s cell types, and secretes
biochemical signals that tell the cells what they have to do at all times. It’s
a kind of regeneration ‘hub’”, states Angel Raya, ICREA Researcher and
director of CMRB.
After a heart
lesion, the epicardium cells begin to divide and move en masse to cover the
wound. Researchers have observed that, during this process, the cells become
binucleated: they duplicate the genetic material and separate it into two
nuclei, but they are not divided into two independent cells. “We were very
surprised to discover cells that, instead of having one nucleus, as is the case
in most tissues, they have two nuclei, and each of them contains a copy of the
cell’s DNA” says Trepat, ICREA researcher at IBEC and associate professor of
the University of Barcelona.
Researchers have
discovered that the mechanism by which cells become binucleated has a
biomechanical origin. Once DNA has already separated into two nuclei, most
animal cells form a contractile ring at its centre. As it contracts, this ring
divides the mother cell into two daughter cells. In the case of the heart cells
of the zebrafish, the study shows that the ring adheres to the fibres of its
environment so that it cannot tighten. The result is that the two daughter
cells cannot separate despite having correctly duplicated their DNA.
“Multinucleation
is a well-known phenomenon in cancer, because it is a cause of genetic
instability. In other words, cancer cells lose control of the proteins they
synthesise and behave pathologically. In the case of the heart of zebrafish,
the multinucleation is physiological and does not seem to cause any problem”,
states Marina Uroz, the article’s main author. The next step will be to study
the role of multinucleated cells during the regeneration of the heart and other
organs.
Dr. Trepat and Dr. Raya are part of CIBER-BBN (Biomedical Research Networking Centre in Bioengineering, Biomaterials and Nanomedicine)
Pere Roca-Cusachs and Antoina Khalil in Lucca during the GRC
Last 5th-10th May was held the 2019 Gordon Research Conference on “Fibronectin, Integrins and Related Molecules” where Pere Roca-Cusachs from IBEC and Antoine Khalil from UMCU presented talks discussing Mechanocontrol results on how mechanical signals and the extracellular matrix regulate cell responses and tumour invasion. During the keynote session titled “Mechanisms and Mechanics of Integrin ECM Connections” Pere Roca-Cusachs gave a talk on “Exploring the Substrate Dependence of Integrin-Mediated Mechanotransduction”. Antoine gave an oral presentation where he described how cell-ECM adhesion regulates the positioning of basal cells and their specification into invasive leader cells during collective invasion of breast cancer organoids.
The Gordon Research Conference was held in Lucca, Italy and is the premier international conference for academic, government and industry scientists interested in understanding how integrins and the extracellular matrix regulate virtually every aspect of cell and tissue function. The program of the conference reflected the interdisciplinary nature of the integrin and extracellular matrix field, spanning different areas of biology from inflammation to mechanobiology, cell migration, stem cells, development, and cancer. During the meeting unpublished data was highlighted and stimulated active discussion among all participants.
The application period opens today until the 8th May 2019, where you can submint an abstract if you are interested in giving a short talk during the summer school.
The application does not guarantee acceptance to the Summer School due to the limited number of participants, an email with the resolution of the applicaton process will be sent on June 15th 2019.
The summer school will be held in La Cerdanya at the Eco-Resort located in Prullans in the Catalan Pyrenees.
The participation fee is 300€ (taxes not included) and includes accomodation in shared double room (from 17th-20th September 2019), full-board, workshops and conferences, leisure activities and shuttle bus from Barcelona to the venue.
IBEC is
hosting two members from the Mechano·Control network. On the one hand, Dimitri
Kaurin, PhD student from Marino Arroyo group at Universitat Politècnica de
Catalunya (UPC) that will be staying at IBEC for at least one year and on the
other hand, Amy Beedle, postdoc from Sergi Garcia-Manyes at Kings College
London (KCL).
Dimitri Kaurin started his stay at Pere Roca-Cusachs’ laboratory in December 2018 and it is planned to be for at least a year. One of the objectives of Dimitri’s stay is to work on a protocol to study cell-cell adhesion using a controlled system based on lipid bilayers of controlled viscosity. “Using AFM technique, we expect to access some information about cell-cell adhesion under force” says Dimitri. In the context of this research he will also visit Manuel Salmeron laboratory in Glasgow University this march to learn some techniques about functionalizing lipid bilayers with cadherins.
Dimitri Kaurin working in the laboratory at IBEC
On the other hand, Amy Beedle arrived this past January to Pere Roca-Cusachs’ laboratory. In the Garcia-Manyes lab Amy was looking at how mechanical forces can trigger conformational changes in individual proteins. Here at IBEC, she wants to incorporate the results at the single molecule level with the cellular level, to try to understand how individual bonds and proteins can contribute to cellular mechanosensing. “My aim is to expand my expertise in single molecule force spectroscopy to a larger cellular context” adds Amy.
Amy Beedle working in the laboratory at IBEC
This is the first time that both UPC and KCL teams meet with IBEC to share skills and ideas within the project’s framework.
EBSA association grants this prize every two years. The last winner of the prize was Philipp Kukura from the University of Oxford in the UK in 2017. The prize recognises an investigator across Europe who has defended his thesis 12 years ago or less and awards him with 2000€ and a medal as well as be expected to contribute an article to the European Biophysics Journal. The decision of the winning researcher is made by the Executive Committee based on scientific excellence, leadership and creativity.
The award ceremony will take place in Madrid during the 12th EBSA 10th ICBP-IUPAP European Biophysics Congress from 20-24 of July. During the congress, Pere will be giving a lecture and receive his Young Investigator’s Prize.
The European Biophysical Societies Association was formed in 1984 as a non-profit making organisation, with the objectives “to advance and disseminate knowledge of the principles, recent developments and applications of biophysics, and to foster the exchange of scientific information among European biophysicists and biophysicists in general”. It is composed of the Biophysical Societies in the European area and is managed by an Executive Committee. EBSA is associated with the international organizations International Union for Pure and Applied Biophysics (IUPAB) and Initiative for Science in Europe (ISE) and owns the European Biophysics Journal.
