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Our tributes to Professor Michael Wakelam, director of the Babraham Institute

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“We have heard with great sadness the tragic news that our dear colleague, Professor Michael Wakelam, director of the Babraham Institute passed away of complications suspected to be due to Covid-19 infection. Professor Wakelam was an active voice on the value of international science. He was always enthusiastic and constructive and he was instrumental for building the  EU-LIFE alliance of research institutes as it is today. As Chair of EU-Life, representing The Institut Curie in the alliance, I could always count on him for input and ideas. Michael’s positive attitude and warm personality were an inspiration for so many of us. His loss is tragic for the scientific community and we will miss him deeply.

Our thoughts go to his family and to our colleagues at Babraham Institute in this difficult moment.

The Babraham Institute has opened a book of remembrance for anyone who would like to share their memories of Michael or tributes to him. Please email these to 

Tribute paid by Dr. Geneviève Almouzni / Research center at the Institut Curie / Head of the Chromatin Dynamics team / Member of the Science Academy in France / Co-Chair of the LifeTime Initiative

Further information: https://www.babraham.ac.uk/news/2020/04/michael-wakelam-1955-2020

News

Histone variant H3.3 residue S31 is essential for Xenopus gastrulation regardless of the deposition pathway

Portrait Geneviève Almouzni

During vertebrate development, H3 histone variants H3.1/2 and H3.3 cannot substitute for each other. It has been a longstanding puzzle, whether this is due to unique properties of individual variants or if it simply reflects their different incorporation pathways  (DNA-synthesis dependent or independent). In Xenopus we demonstrated that only the presence of serine at the position 31 (S31) in H3.3 was essential at gastrulation, independent of the incorporation pathway. Moreover, the phosphorylation at S31 promotes acetylation at lysine 27, thus contributing to an open chromatin state. These findings illustrate how a unique residue in H3.3 allows the establishment and the maintenance of particular chromatin states, which are important during cell cycle and development.

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Magnetically focussed proton minibeams : new hopes for radiation therapy!

Yolanda Prezado - PedroLombardi - Science

Proton minibeam radiation therapy (pMBRT) is a novel therapeutic strategy that has proven to significantly increase dose tolerances and sparing of normal tissue, while achieving tumor control equivalent to or better than conventional radiotherapy in high-grade gliomas in small animals. pMBRT uses submillimetric proton beams, about an order of magnitude smaller than the beams used in clinical practice. The current implementation of pMBRT with mechanical collimators, although valid,  has shown its limits: rigidity, reduction in efficiency and production of additional secondary neutrons.

One potential solution, explored by the new SIRIC team New approaches in Radiotherapy headed by Yolanda Prezado UMR3347 / U1021 is the generation of proton minibeams by magnetic focusing. With that aim they have designed a new optimized nozzle which could be integrated at existing clinical centers. This design uses conventional beamline elements and has a moderate focal length of approximately 1 m and a shortened air gap of 10 to 30 cm. This new nozzle is capable of providing beam sizes between 0.66 and 1.67 mm FWHM at clinically relevant energies.

It can therefore be considered appropriate for pMBRT, leading to an optimal implementation of pMBRT. It could allow a more effective and flexible treatment, accessible to 3D intensity modulated treatments. This is a major development in the project that approaches pMBRT a step closer to patients’ treatments.  A patent has been filed.

 

Learn more https://www.nature.com/articles/s41598-020-58052-0

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New International PhD Program: Ready? Steady? Apply now!

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Within the frame of Institut Curie’s new PhD Program called EuReCa, 8 positions are offered by Institut Curie’s research teams. The call for applications is now open. The 8 laureates will join their PhD laboratory in September 2020.

Cofounded by the European Commission, EuReCa (Europe, Research & Care) is Institut Curie’s new excellent interdisciplinary, inter-sectorial, and international PhD Program. Candidates wishing to apply must complete an online application form via the EuReCa webpage before January 9th, 2020, 4:00pm CET.

Following the closing date of the call, a Review Board composed of internal and external scientific experts will score and rank the eligible applications.

For each project, 3 to 4 shortlisted candidates will be invited for an interview session on May 27-29 2020. The interview will be led by a Selection committee composed of the future Thesis Director and scientific experts (one internal to Institut Curie, one external).

The 8 laureates will join their labs on September 1st, 2020.

Find the list of projects, the calendar and all the information here! (a link to share without restraint!).

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Invacell: Philippe Chavrier and Harald Stenmark labs received grant to collaborate on cancer invasion and metastases research

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Philippe Chavrier and his colleagues have received a joint grant with Norwegian researchers from the group of Harald Stenmark from The Institute for Cancer Research, Oslo University Hospital, Oslo, Norway. The funds were donated by Trond S. Paulsen and allocated by The Radium Hospital Foundation to combat cancer cell invasiveness through the project Invacell.

The project is a basic research work that facilitates the development of drugs in the long term that can prevent the spread of metastases. The research will run over four years and contribute to strengthening the long-term cooperation between Norway and France. The project has been created simultaneously with a newly established framework agreement for cancer research between Oslo University Hospital and Institut Curie.

Philippe Chavrier and his colleagues at Institut Curie have long-standing interest in understanding the mechanism of tumor invasion in breast cancer. Their studies on MT1-MMP and invadopodia in breast cancer invasion were crucial contributions to the foundation of the collaboration.

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The physicist Pascal Hersen, new director of the Curie Physical Chemistry unit

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Pascal Hersen, CNRS director of research in biophysics, has taken over as director of the Curie Physical Chemistry unit (UMR 168 CNRS/Institut Curie). Following a call for tenders, his application was supported by an international recruitment committee and by the Scientific Advisory Board of Institut Curie, and approved by the director of the Research Center. He replaces Axel Buguin, interim director of the unit following the sudden death of Maxime Dahan in 2018.

Until now, Pascal Hersen (PhD), 42 years old, headed an interdisciplinary team of around fifteen researchers at the Laboratoire matière et systèmes complexes in the Physics Department at Université Paris Diderot. His work is in a new field of research – cybergenetics – which involves determining how cells process information, how they adapt dynamically to changes in their environment and to what extent it is possible to control the cellular processes. This physicist joins the Institut Curie Research Center to head up the Curie Physical Chemistry unit (UMR 168 CNRS/Institut Curie).

The work of the Curie physical chemistry unit, whose aim is to propose a physics-related vision of the fundamental processes at work in living cells, using methods and concepts from experimental and theoretical physics, and the work in the field of cybergenetics conducted by his team joining the unit, will be mutually enhanced. “We are developing computerized feedback loops to control the level of gene expression in real time at the single-cell level. This new technological approach combines microfluidics, microscopy, synthetic biology, optogenetics and theory of control,” he explains, “and we are looking to determine whether or not to apply this approach to a variety of contexts from controlling gene expression in single cells to spatial orchestration of multicellular dynamics.”

“Within the unit, and without prejudice to the interactions with the other research units, a great many collaboration projects are taking shape,” comments Prof. Axel Buguin, interim director of the unit since the death of Maxime Dahan last July. “The research subjects perfectly match those developed in the unit involving quantitative biology. They will benefit from our involvement in the Institut Pierre-Gilles for microfluidics.” For one year, Prof. Buguin, who was deputy director alongside Maxime Dahan, worked tirelessly to manage the transition and prepare for the future of the research unit and the some 120 people working there. It has been decided that Mathieu Coppey, head of the Cellular organization and imaging team (LOCCO), will be the unit’s deputy director.

Encouraged by meetings with team leaders in the unit, as well as with most of the research unit directors on the Paris site of the Research Center, the new unit director was able to observe the “wonderful interdisciplinary and collaborative approach, as well as a rich ecosystem of resources and researchers. Within this exceptional context, the unit will strive to contribute to the Curie research-care continuum model by developing innovative research projects focused on the physics of cancer, from understanding the elementary behavior of cells and tissues, to the medical applications.”

Pascal Hersen has authored over 40 peer-reviewed publications, filed two patents and helped create a start-up. He is the beneficiary of an ERC Consolidator grant (SmartCells). He was involved in founding the Centre de recherche interdisciplinaire (CRI), today attached to the University of Paris, and was auditor for the Institut des hautes études pour la science et la technologie (IHEST).

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A new player in the regulation of epigenetics

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The team of Raphael Margueron, together with that of Deborah Bourc’his and other international teams, highlighted the role of a new key player in the regulation of genes and its dysfunction that can lead to different diseases.

Gene expression, i.e. the control of their use by a given cell at a given time, responds to complex mechanisms. A group of proteins called Polycomb contributes to the orchestration of genes, reducing them to silence when they should be inhibited by the phenomenon called epigenetics. “In mammals, the “Polycomb machinery” is composed of dozens of proteins,” says Raphael Margueron, researcher at Institut Curie (U934 INSERM/CNRS UMR3215). His team is taking a close interest in this group and other players that are moving around to indicate to the Polycomb group proteins which genes should be blocked from expression.

In this context, Raphael Margueron and his colleagues have worked to highlight the role of a previously unknown player in these processes: EZHIP. Its intervention is necessary for the maturation of female gametes (reproductive cells). Their discovery published in Nature Communications comes at the same time that other teams have revealed the role of EZHIP in many types of children’s brain cancer. Highlighting their scientific and medical interests, these different revelations were put into perspective in the Nature journal where the authors note that “these studies lay the groundwork for exploring the role of this protein in triggering cancer and indicate that targeting PRC2 or EZHIP may have therapeutic potential for children with [these cancers]”. With these promising advances, “we will continue to study this co-factor to understand why it is so important,” promises Raphael Margueron.

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A “molecular motor” reveals unsuspected strengths

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Anne Houdusse, a specialist in “molecular motors” at Institut Curie, revealed in Nature Communications a new mode of action of these motors involved in malaria infection. A disease that annually kills half a million people worldwide.

For over 25 years Anne Houdusse (UMR 144 CNRS / Institut Curie) has focused her research on molecular motors: proteins capable of developing mechanical forces and producing movements. It is through these molecular motors that our muscles contract, for example, but it’s also thanks to them that cancer cells can be triggered to metastasize…
The researcher has become an international reference on the subject. The proof? “When several scientists in the United States and England began to suspect the involvement of one of these molecular motors, Myosin A, in the infection with Plasmodium [the malaria parasite], they contacted each other simultaneously,” she explains. The researchers then organized themselves into a consortium and revealed the precise role of Myosin A in this context.

“Experts in visualizing motors at atomic resolution, we also gained expertise in the development of small molecules to block the operation of these engines. Our goal is to understand their role in health and disease,” she further explains. In the case of the Plasmodium Myosin A, we uncovered the details of its atypical mechanism for force generation. We understood how the motor can adapt the force produced for different essential functions of the parasite: the invasion of red blood cells and the rapid spread of the parasite to other stages of its cycle. ” These results make it possible for us to develop new treatments against malaria by targeting the key driver – Plasmodium Myosin A.

Sources

Plasmodium myosin A drives parasite invasion by an atypical force generating mechanism

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Intestinal homeostasis and active cell migration

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Active cell migration would appear to play a crucial role in homeostatic renewal in the adult intestinal epithelium according to the findings to come out of a new study published in Science and conducted by Denis Krndija, a researcher in Danijela Matic Vignjevic’s team at the Research Center. These findings open up new possibilities in regulating this complex homeostatic process, and disruption triggered by cancer.

Drawing on a combination of biophysical modelling and 3D quantitative tissue imaging, as well as physical and genetic manipulations in mice, Denis Krndija and his co-authors from the cell invasion and migration team overseen by Danijela Matic-Vignjevic at the Research Center and in collaboration with Edouard Hannezo (Institute of Science and Technology, Austria) uncovered the existence of a migratory force active during homeostatic* epithelial renewal, in findings published in the Science journal. “This active migratory force is dependent on actin cytoskeleton dynamics induced by the Arp2/3 protein complex, a key factor in actin nucleation”, explains post-doctoral researcher Denis Krndija. The team analyzed cellular speed and tissue tension and density along the intestinal villi in order to quantitatively determine the equilibrium of both mitotic and active migratory forces in epithelial homeostasis. They demonstrated that mitotic pressure has a limited, short-range effect, restricted to the lower areas of the intestinal villi, where cells migrate more slowly. In the rest of the villi, however, cells migrate actively, using cellular protrusions.

However, according to CNRS team leader Danijela Matic-Vignjevic (UMR144 CNRS/Institut Curie cellular biology and cancer), “if this complex homeostatic process isn’t properly controlled, it can lead to high probability of failure, therefore resulting in pathologies such as tumors and inflammatory diseases”. The translational impact of this research was further explored by Dr. Marnix Jansen (University College London, United Kingdom) in the same issue of Science, offering up new prospects in research into colorectal cancer.

Over and above the key role it plays in absorbing nutrients, the intestinal epithelium serves as a barrier against bacterial, biochemical and mechanical attacks in its lumen’s harsh environment. The small intestine’s epithelium comprises a single layer of cylindrical cells that cover the intestinal villi, projections that protrude out into the intestine’s lumen, as well as crypts, small invaginations in the underlying connective tissue containing stem cells.

Cell migration at the heart of intestinal homeostasis

All epitheliums are continuously self-renewing, powered by mitotic stem cell division. According to Denis Krndija, “the intestinal epithelium is the body’s fastest self-renewing epithelium – we get a brand-new epithelium every week!”. The cycle starts via cell division in the crypts, after which the cells migrate upwards along the villi. Cell migration is therefore a key process in epithelial renewal. It had previously been thought to be a passive process, induced by the force generated by cell division in the crypts.

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Active cell migration is critical for steady-state epithelial turnover in the gut 

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Fevrier 26 - Mars 4, 2020

NON-CODING GENOME

Institut Curie
Organizer (s)

Sven Diederichs (Albert-Ludwigs-University Freiburg,  DE)

Antonin Morillon (Institut Curie, FR)

Marina Pinskaya (Institut Curie – Sorbonne Université, FR)

 

Scientific committee:

Déborah Bourc’his (Institut Curie, FR)

Maiwen Caudron-Herger (German Cancer Research Center DKFZ, Heidelberg, DE)

Ines Drinnenberg (Institut Curie, FR)

Arturo Londoño (Institut Curie, FR)

Alena Shkumatava (Institut Curie, FR)

Maxime Wery (Institut Curie, FR)

This course will explore the versatility of non-genic DNA elements and non-coding RNAs across a spectrum of cellular processes, in humans and model organisms, and their implication in physiology and disease. Internationally recognized experts will present their latest findings related to the identification and functional characterization of the non-coding genome and discuss novel concepts in genome regulation and evolution, with a strong emphasis on experimental and computational tools. Thematic sessions will include long and small non-coding RNAs, transposable elements, structural DNA repeats and non-coding regulatory elements. This course will offer to young students and research fellows the opportunity to broaden their knowledge and discuss their work with an international scientific community in a warm and stimulating environment at the Institut Curie in Paris.

 

Application deadline: December 1, 2019

Please, register here!