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2023 YEAR IN REVIEW

Cover: Human colonic organoid by Marius Mählen (Liberali lab)

Foreword In 2023, the FMI has continued to generate new scientific knowledge that may guide drug discovery efforts and lead to new ideas of drug targets. Our researchers published more than 100 studies — a few of which are highlighted in this brochure — in international scientific journals. The year also marked the 25th anniversary of the institute’s International PhD program, a flagship program that has trained over 700 hundred doctoral students to become leaders in academia, industry, and other sectors. As an institute made of diverse research teams, we are committed to fostering an inclusive work culture and scientific research environment. In 2023, we took further steps towards the development of a strategic approach to Equality, Diversity, and Inclusion. To provide our researchers and support staff with an environment that is engaging and stimulating, we also offer a variety of social events and activities, some of which are highlighted in this brochure. We believe that now more than ever it is crucial to ensure wider awareness of the importance of research by the public. That’s why we strive to inspire and inform a wide range of audiences through communications and outreach activities. Last year, for example, our researchers and staff have engaged with several groups of young visitors, offering them unique insights into a career in research. As 2023 winds down, the FMI is preparing to leave its old premises in Kleinbasel. In 2024, the institute is set to relocate across the Rhine to its new state-ofthe-art home on the Novartis campus. The much-anticipated move will bring our researchers closer to their Novartis colleagues, boosting opportunities for scientific exchange and new collaborations.

JANUARY

Identified: components of the molecular clock that helps some animals shed their skin Shrimps, flies, and other animals shed their outer body covering at specific times of the year or at specific points in their life cycles through a process called molting. Working in worms, researchers in the Grosshans lab identified the mechanisms underlying a molecular ‘molting clock’ — as well as several of the clock’s components. The findings may help to throw light on skin development and regeneration in other animals, including mammals. Meeuse et al., EMBO Journal 4

FEBRUARY

Hiring new group leaders Hiring a new research group leader is an important undertaking at the FMI since a group leader — and the type of research they are conducting — will influence the long-term strategy of the whole institute. This year the FMI embarked on the recruitment of two new group leaders, one in structural biology and one in multicellular systems. Towards the end of the year, we had the pleasure to announce that Selma Dahmane, currently a postdoctoral researcher at the University of Umea, Sweden will join us in spring 2024.

Translating an RNA boosts its degradation In the cell, messenger RNAs — or mRNAs — are translated into proteins and eventually degraded, but the relationship between translation and mRNA decay remains cloudy. Researchers in the Chao group developed an innovative tool to control and visualize mRNA translation and decay, one molecule at the time. The team discovered that translation promotes mRNA degradation — a finding that may help advance the development of RNA-based drugs. Dave et al., Molecular Cell 5

Chess & Cheese Among the various social events organized at the FMI, “Chess and Cheese” has become very popular. The event, which took place three times in 2023, brings together chess aficionados who compete in a tournament while enjoying a selection of fine cheeses and wine. The atmosphere at these events is so nice that people don’t mind losing a game in four moves, as reported by a participant!

Supporting women in science The FMI is a founding member of TWIST (Towards more Women in Science and Technology), a network of local academic research institutes that supports the advancement of women in science with seminars and networking opportunities. After TWIST’s activities paused because of the COVID pandemic, the network was relaunched this March with an event that took place at the FMI. In November, the FMI hosted another TWIST event, which allowed up-andcoming female researchers to showcase their work and connect with leading female scientists in Basel’s biomedical research community.

MM AR AC YH

The FMI PhD Program turns 25 For the past 25 years, the FMI has been training over 700 hundred doctoral students to become future leaders in academia, industry, and other sectors. Since 2016, we also offer an MD-PhD Program that provides research-oriented medical students and physicians with the opportunity to carry out fundamental biomedical research. In 2023, our institute continued to receive excellent applications from around the world and selected successful applicants through a recruitment process that involved in-person interviews on site.

APRIL

Sharing our passion for DNA April 25, 2023 marked the 70th anniversary of a few iconic research papers on the structure of DNA, published in the journal Nature by James Watson, Francis Crick, Maurice Wilkins, Rosalind Franklin and colleagues. To celebrate this anniversary, the Kirschgarten Gymnasium — one of the biggest high schools in Basel — gave its students the opportunity to learn more about DNA at various local institutes, university departments and companies. At the FMI, we welcomed more than 100 students and shared our passion for the “molecule of life” with them.

A journey into the world of DNA To celebrate the 70th anniversary of the discovery of the DNA double helix, FMI Director Dirk Schübeler gave a “Behind the science” lecture at the Novartis Pavillon — a learning, event and exhibition space on the Novartis Campus that is open to all and explores the big questions around healthcare. Schübeler took the audience on a journey into the fascinating world of DNA and gene technology.

Revealing how an embryo’s cells sync up Scientists have known that when a mouse embryo is developing, the cells that will become its spine and muscles switch specific genes on and off repeatedly, in a synchronous fashion. However, there are deep mysteries about how these cells synchronize. Researchers in the Tsiairis lab have now developed a mathematical model that not only better explains how spontaneous synchronization arises in a developing mouse embryo, but it may also offer some fundamental clues about how other biological systems sync up. Roth, Misailidis et. al, Development Cell

MAY

Holding it all together FMI administrative staff are rarely in the spotlight, but they make our institute run. In May, staff from different administrative teams, including People & Organization, Finance, Facility Management and more, got together for their yearly outing, which featured a visit of the Novartis Pavillon and a tasty dinner at a new restaurant nearby.

Students become scientists for a day For the past 25 years, the FMI’s “Tage der Genforschung” (Days of genetic research) have attracted high-school students from northwestern Switzerland and neighboring regions in Germany. The event is aimed at stimulating the interest of students in a career in research. In 2023, nearly 200 students and their teachers visited our institute to learn firsthand from FMI group leaders, postdocs and students what it means to be a biomedical researcher. 11

MARCH

Embryo-like models help map early stages of development An organism’s body plan arises through a process called gastrulation, during which the embryo forms three distinct layers of cells that will later give rise to all organs. Now, researchers in the Liberali lab have mapped the development of three-dimensional clusters of cells that mimic aspects of gastrulation, providing important insights into the molecular mechanisms that regulate early embryonic development and cell fate determination. Suppinger, Zinner, Aizarani, Lukonin et. al, Cell Stem Cell

AJPURNI EL

Celebrating 10 years of advocacy for research excellence EU-LIFE is an alliance of leading European research centers in life sciences whose goal is to advocate for research excellence in Europe. The FMI joined the alliance shortly after it was created in 2013. This year marked the 10th anniversary of EU-LIFE, a milestone that was celebrated with a conference entitled “Envisioning the research centers of the future”. A small delegation from the FMI attended the event, which brought together scientists, politicians, leaders, and administrative staff of research institutions from all over Europe.

Building face structures by remote control Craniofacial birth defects, including cleft lip and palate, are among the most common human congenital malformations. Now, researchers in the Rijli group have identified a DNA region containing multiple regulatory elements that interact with genes across distant chromosomal neighborhoods, ensuring that specific facial structures develop in the right place. The findings may provide new insights into normal head development as well as craniofacial birth defects. Sandra Kessler, Maryline Minoux, Onkar Joshi, Yousra Ben Zouari et. al, Nature Communications 13

From left to right: Our alumni — Marietta Hartl, Dominik Hartl, Aneliya Rankova, Dominik Kraus, Aline Xavier da Silveira dos Santos, Florian Aeschimann — and event organizer Piera Cicchetti, FMI Guidance Counselor

Alumni Career Seminar Every year, the FMI organizes a career event with its alumni and alumnae — many of whom are thriving in academia or industry. In 2023, we invited six former FMIers who went on to pursue a career in industry to tell us about their work. The talks were followed by round tables and a lively apéro session with FMI PhD students and postdocs.

Zeroing in on how the ‘guardian of the genome’ works The tumor suppressor protein p53 has been dubbed the ‘guardian of the genome’ because it protects the DNA from stress or long-term damage by regulating the expression of numerous genes involved DNA repair, cell division and cell death. Now, researchers in the Schübeler lab have homed in on some of the mechanisms that regulate the activation of p53 target genes. Isbel et al., Nature Structural & Molecular Biology 14

Promoting Equality, Diversity and Inclusion At the FMI, we are committed to fostering a more inclusive working and research environment that attracts people of diverse backgrounds and helps them to thrive. This year, we took steps towards the development of a strategic approach for Equality, Diversity and Inclusion (EDI) with clear deliverable actions. First, we appointed Roshni Mooneeram, a senior consultant in the governance and strategic management of EDI, as an external consultant. With her help, we set up a governance structure, consisting of an EDI Committee and EDI board, that will help translate good intentions in EDI into actions. Both bodies met several times this year, discussing challenges, opportunities, and possible solutions. A first outcome was a training in inclusive leadership for all FMI staff in manager roles.

Roshni Mooneeram talking to FMI associates about equality, diversity and inclusion in science

J U LY

Social media milestone

Luca Giorgetti elected an EMBO member Group leader Luca Giorgetti was elected a member of the European Molecular Biology Organization (EMBO) — a prestigious recognition for scientists in Europe and beyond for their research excellence and outstanding achievements. Giorgetti had already been awarded a prestigious Consolidator Grant from the Swiss National Science Foundation (SNSF), which he will use to study the fundamental principles that govern enhancer biology. SNSF’s Consolidator Grants are transitional funding measures put in place by Switzerland after the country dropped out of the European Union’s research program Horizon Europe. 16

Since 2017, when the FMI joined Twitter, our followers have grown on a steady basis. In July 2023, we reached 5,000 followers on the social media platform, now called X. We are looking forward to sharing our exciting science, news & events, job opportunities, and the occasional lab joke, with many more followers in the coming years. The FMI is also on LinkedIn, Instagram, YouTube, Facebook and TikTok.

Mouse study sheds light on how antipsychotics work Antipsychotic drugs are used to treat and manage symptoms of many psychiatric disorders, but their mechanisms of action remain a mystery. Researchers in the Keller group have found that antipsychotics reduce long-range communication within a specific layer of the brain cortex — a finding that may explain how these medications work. Heindorf & Keller, eLife

AUGUST

Swimming in style Last year, the FMI refreshed its look with an updated logo, colors and font. In the first half of 2023, the new visual identity was implemented across digital and print. Among the rebranded items were swim bags called “Wickelfisch”. During the summer, many of these FMI-branded swim bags could be seen floating down the Rhine river.

SEPTEMBER

Grit and grind Sport fans at the FMI meet regularly to practice various kinds of activities together. Particularly noteworthy is our FMI football team, who has achieved great feats in the past. This year again, our institute footballers competed in the “Novartis Cup” and the “Science Cup”, two popular local tournaments. Although the FMI team didn’t bring any award home this time, they played hard and showed amazing teamwork.

FMI Annual Meeting 2023 Our institute’s annual retreat, which brings together FMI scientists and several colleagues from Novartis, took place in the renown Alpine resort Davos. The dense program included scientific talks by postdocs and PhD students, a plenary lecture by Ibrahim Cissé, Director at the Max Planck Institute of Immunobiology and Epigenetics in Freiburg, two poster sessions, an award ceremony for the FMI internal science prizes and a gala dinner with entertainment. Participants also had the chance to take part in excursions around Davos.

OCTOBER

How AI can help uncover the way memory works

A symphony of electrical signals and a dynamic tangle of connections between brain cells help us to make new memories. Using AI-powered models of groups of neurons, researchers in the Zenke group are working towards unlocking how the brain orchestrates this dance. One of their latest studies, published in October, achieved a major advance in accurately simulating the changes in the connections between neurons that sense the external environment, opening the door to a greater understanding of how countless brain cells transform sensations into perceptions and thoughts. Eventually, AI-powered tools may help to illuminate some of the workings of real brains. Halvagal & Zenke, Nature Neuroscience

N OAVPERMI LB E R

Celebrating the Festival of Lights At the FMI, people from 43 nationalities work hand-in-hand, so everyone has a privileged access to different cultures and customs. This year, the Indian community at our institute organized a celebration of Diwali, the Festival of Lights — one of India’s biggest holiday representing the triumph of good over evil. The well-attended event included tasty snacks, festive decoration, and traditional clothes and music.

DECEMBER

New home coming soon The long-awaited move to a new building on the Novartis campus is just around the corner. In spring 2024, our institute will relocate to a former production building that has been fully remodeled to meet the FMI needs. The goal is to unite all our staff, including those working in the animal facility, under one roof. The new building — equipped with state-of-the-art labs, office areas, and plenty of meeting spaces — is called “Fab 24”. The architects, planners and builders went full throttle this year to complete the building.

Expectation vs. Reality: study maps the neurons that tell the difference When our expectations differ from reality, specific sets of brain cells are activated. Working in mice, FMI researchers in the Keller group have characterized these neurons based on their gene-expression patterns, paving the way for a better understanding of some of the neuronal deficits associated with neuropsychiatric conditions. O’Toole et al., Neuron

It’s the end of the year — let’s party! The last FMI Year-End Party in the old building was celebrated in the traditional way — with FMIers, their families, and retirees. Kids animations, the Director’s year-end update, a cake competition, a quiz, and plenty of food and drinks made for a great evening.

FACTS & F I G U R E S

FMI Staff (December 1, 2023) Research group leaders (19)

Visiting scientists and temp (32)

Administration, Building, Services (26)

338

Research Associates (38)

Postdoctoral fellows (71)

PEOPLE of

NATIONALITES

PhD students (84)

Technical Platforms Associates (56) Undergraduates (12)

Research Groups GENOME REGULATION

MULTICELLULAR SYSTEMS

Marc Bühler Jeffrey A. Chao Guillaume Diss Luca Giorgetti Dirk Schübeler Nicolas Thomä*

Helge Großhans Prisca Liberali Patrick Matthias Antoine H.F.M. Peters Charisios Tsiairis Margherita Yayoi Turco

NEUROBIOLOGY Silvia Arber Johannes Felsenberg Rainer W. Friedrich Georg Keller Andreas Lüthi Filippo Rijli Friedemann Zenke

* transitioning to the EPFL 27

FACTS & F I G U R E S

Awards, Grants and Fellowships 2023 STUDENTS & POSTDOCS Aleena Garner → FMI Max Burger Prize Zuzanna Kozicka → F MI Ed Fischer Prize → European Federation for Medical Chemistry – Young Scientists Network PhD Prize → I ncluded in Forbes’ Science & Healthcare “30 Under 30” Europe list → Science & SciLifeLab Prize for Young Scientists Agata Misiaszek → EMBO Postdoctoral Fellowship Konstantinos Ntitsias → Boehringer Ingelheim Fonds PhD Fellowship Jan Seebacher and Charlotte Soneson → FMI Ruth Chiquet Prize András Szőnyi → University of Basel Research Fund Junior Researchers

GROUP LEADERS Rainer Friedrich → SNSF Project Funding Grant Luca Giorgetti → SNSF Consolidator Grant; EMBO membership Helge Großhans → SNSF Project Funding Grant Georg Keller → SNSF Project Funding Grant Filippo Rijli → SNSF Project Funding Grant Nicolas Thomä → SNSF Project Funding Grant

FACTS & F I G U R E S

PhD Thesis presented in 2023 Alexandra Bendel (Diss group) → From Mutations to Meanings: Using Deep Mutational Scanning to understand sequence-function relationships through protein-protein interaction specificity Eleonora Castelli (Peters group) → Maternal modulation of Polycomb function during mouse embryonic development Bastian Eichenberger (Chao group) → Applications of deep learning in biology Maike Graf (Großhans group) → Unraveling the spatiotemporal organization of a developmental oscillator Sandra Kessler (Rijli group) → Role of long-range super-enhancers in craniofacial morphogenesis Marlena Lübke (Schübeler group) → Characterization of regulators of CpG island activity in mouse stem cells

Pia Mach (Giorgetti group) → The role of loop extrusion in the dynamics of chromosome folding Maria Pappa (Tsiairis group) → Rac1 small GTPase regulates oscillation dynamics during mouse embryo segmentation Vittoria Peretti → A dedicated cortico-hippocampal network changes the behavioral output of learning ensembles in the striatum Param Valiathan (Caroni group) → Cortico-Thalamo-Hippocampal networks in alternative learning Baba Yogesh (Keller group) → The problem of perception – Insights from beer-drinking, acetylcholine, and Alzheimer’s Gloria Zaina (Arber group) → Shared engagement deficit phenotype and circuit-mechanism in four mouse models of Autism Spectrum Disorders.

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Friedrich Miescher Institute for Biomedical Research Maulbeerstrasse 66 4058 Basel Switzerland Phone: +41 61 697 66 51 E-mail: office@fmi.ch