Organismal Systems Biology
Organismal Systems Biology Lab
Research
Animals consist of thousands of different types of molecules. To comprehend this immense complexity, we search for fundamental design principles of molecular circuits at a multi-cellular scale. To this end, we combine theory and quantitative experiments using the nematode C. elegans.
Our research asks:
1. how the many cells of an animal coordinate their growth to faithfully produce an appropriate body plan (developmental robustness),
2. how cells respond to nutritional conditions to adjust organismal phenotypes to the current environment (developmental plasticity).
Technologically, we specialize in live imaging of C. elegans in micro chambers to make precise measurements of its development and gene expression. By genetic perturbations, we test and refine quantitative models of animal development.
1. Do animals find an optimal balance between growth and aging?
Environmental conditions affect the rates of growth and aging. Most famously, animals delay aging when environmental nutrients are scarce, and grow more slowly. We want to understand if this control of growth and aging increases the long term evolutionary success of a genotype, or is merely a passive consequence of a slow metabolism.
Our research builds on mathematical models of life history theory stating that animals face tradeoffs between growth and aging and need to balance their investment between these two tasks. Specifically, theory predicts that a different compromise between growth and aging is optimal in different nutritional conditions.
Using genetics, we experimentally modulate the rates of growth and aging of C. elegans to test these theoretical predictions. We ask which balance between growth and aging presents the best compromise and study the molecular mechanisms by which animals compute optimal tradeoffs in different environments.
We believe that this research will unravel functions of metabolic signalling networks that are only apparent when studied at the scale of an entire animal or even population.
Mathematical model of tradeoff between growth and aging
A mathematical model predicts that under poor nutritional conditions animals have a selective benefit by shifting their investment from promoting rapid growth to delaying aging. We are testing this model prediction experimentally.
2. How do animals reach the right size and proportions?
Genetically identical individuals never look completely the same due to the stochasticity of biological processes. We want to understand how animals prevent that small differences among individuals at birth amplify to much larger differences during the development of an animal. Specifically, we focus on the relation between heterogeneity in growth, organ and body size of C. elegans.
In principle, two individuals that differ even only slightly in their growth rate are expected to differ increasingly in their body size during development due to the exponential nature of growth. This effect is comparable to small differences in the interest rate on a bank account that over the years amplify to large differences in savings due to the benefit of compound interest.
We ask how animals maintain a constant body size despite heterogeneity in their growth rate. To address this question, we use micro chambers to grow hundreds of individuals of C. elegans in parallel (see movie here) and track each individual's rates of growth, development and size.
Individuals of C. elegans growing in arrayed of micro chambers.
Principal investigator
Benjamin carried out a PhD in Genetics with Prof. Susan Gasser at the FMI in Switzerland, where he studied epigenetic mechanisms of gene control using C. elegans. As a postdoc, he joined the group of Prof. Uri Alon at the Weizmann Institute in Israel, studying optimality principles in bacterial growth control. Since November 2019, he has been an SNSF Eccellenza Professor at the University of Bern. In his lab, he applies quantitative systems biology approaches to study optimality principles at a multi-cellular scale using C. elegans.
Klement Stojanovski, PhD
Lab manager
During his PhD, Klement studied prion formation, using S. cerevisiae. He continued working with yeast as a postdoc studying a kinase signalling pathway, before switching to mammalian cell cultures to study drug targets in the endocannabinoid system. In our group, he studies body size homeostasis and makes sure that everything runs smoothly in the lab.
Peter Lenart, PhD
SNSF Swiss Postdoctoral fellow (MSCA replacement)
During his PhD, Peter developed his primary expertise in theoretical and computational biology, focusing mainly on the evolution of aging. He also acquired a rich experience in interdisciplinary research that ultimately led him to the decision to return to lab work so he could experimentally test his theoretical concepts. In our group, Peter studies the information contained in the developmental trajectories of individual C. elegans and asks various evolutionary questions along the way.
Joel Tuomaala
PhD student
Joel is a Finnish student with an MSc in Animal Physiology and Genetics from the University of Turku. He previously worked with cellular senescence and C. elegans proteomics. In his PhD project, he uses C. elegans to study metazoan growth laws and the regulation of growth and aging.
Sigma Pradhan
PhD student
Sigma comes from India with graduation from IISER Kolkata. She did her masters on regulation of HER2-induced oncogenicity and HER3 expression in breast epithelial cell lines at IISER Pune. Her interest in interdisciplinary sciences led her to organismal systems biology lab. During her Ph.D. she is studying the parental effects of dietary restriction in C. elegans on ribosome expression and growth dynamics, and the regulatory mechanisms involved.
Ioana Gheorghe
PhD student
Born in Romania, Ioana obtained her Bachelor of Science in Molecular Life Sciences from Radboud University in the Netherlands, where she worked with S. lycopersicum plants on reproductive heat tolerance. She chose to continue her studies in Molecular Life Sciences at Bern University, focusing on the coordination of tissue growth during C. elegans development in her MSc thesis and stayed for PhD.
Julie Perey
MSc student MLS
Julie joined us after a BSc in Biology at the University of Bern to do her MSc research. She is working on optimality principles and tradeoffs in organismal growth control.
Noelia Gerber
MSc student MLS
Noelia obtained her BSc in Biology at the university of Bern and joined the lab for her MSc research. She is studying the tissue growth coordination via insulin signaling during C. elegans development.
Urs Nösberger
MSc student MLS
After graduating as a BSc in Biology at the University of Bern, Urs joined the lab for his MSc research. Together with Joel Tuomaala, he studies metazoan growth laws and how ribosome levels are controlled under starvation.
Sacha Psalmon
Computational scientist
Born in France, Sacha is an engineering student at the Polytech Nice-Sophia engineering school. Specialized in Applied Mathematics and Modelling, he is developing new image analysis pipelines using neural networks, and analysing mathematical models on the evolution of ageing.
Alumni
Artur Luzgin (internship)
Franziska Schmid (MSc, MLS)
Aaditya Saxena (BSc, ThinkSwiss scholar)
Stefano von Wyttenbach (BSc)
Garima Yadav (MSc intern)
Team
Benjamin Towbin, PhD
Selected Publications
Growth and size control
2022, bioRxiv (preprint)
Klement Stojanovski, Ioana Gheorghe, Anne Lanjuin, William B Mair,Benjamin D Towbin
2022, bioRxiv (preprint)
Martijn Wehrens, Laurens H.J. Krah, Benjamin D. Towbin, Rutger Hermsen, Sander J. Tans
2022, Nature Communications
Klement Stojanovski, Helge Großhans & Benjamin D. Towbin
2018, Cell reports
Yael Korem Kohanim, Dikla Levi, Ghil Jona, Benjamin D Towbin, Anat Bren, Uri Alon
2017, Nature Communications
Benjamin D Towbin, Yael Korem, Anat Bren, Shany Doron, Rotem Sorek, Uri Alon
2016, Scientific reports
Glucose becomes one of the worst carbon sources for E.coli on poor nitrogen sources due to suboptimal levels of cAMP
Anat Bren, Junyoung O Park, Benjamin D Towbin, Erez Dekel, Joshua D Rabinowitz, Uri Alon
Epigenetics and Chromatin
2015, Cell
Adriana Gonzalez-Sandoval, Benjamin D Towbin, Veronique Kalck, Daphne S Cabianca, Dimos Gaidatzis, Michael H Hauer, Liqing Geng, Li Wang, Teddy Yang, Xinghao Wang, Kehao Zhao, Susan M Gasser
2012, Cell
Benjamin D Towbin, Cristina González-Aguilera, Ragna Sack, Dimos Gaidatzis, Véronique Kalck, Peter Meister, Peter Askjaer, Susan M Gasser
2009, Current Opinions in Genetics & Development
Benjamin D Towbin, Peter Meister, Susan M Gasser
Join us!
PostDocs: We are always interested in motivated talent and can explore possible projects and funding opportunities, including postdoctoral fellowships from EMBO, MSCA, HFSP, or FEBS. Please get in touch by email providing your CV, a motivation letter, and a statement of research interests.
PhD students: We currently have funding available for a PhD student. Please get in touch if you are interested by sending an email with your CV and a cover letter describing:
(i) who you are
(ii) what you hope to learn/achieve by doing a PhD
(iii) what makes you interested in my lab.
Undergraduates (MSc/BSc): Please get in touch by email for training opportunities. We usually have wet or dry lab projects available. Include a CV and a cover letter with brief statement of your research interests (e.g. a lecture topic you particularly liked during your studies). Undergraduates from Europe (except Switzerland) can be funded through the SEMP/Erasmus program. International students may e.g. apply to the ThinkSwiss or ThinkSwiss-Asia programs
Worm cinema
Individuals of C. elegans growing in micro chambers
Individual animals of C. elegans were recorded simultaneously in arrayed micro chambers from birth to adulthood at a time resolution of 10 minutes.
Worm race
Individuals of C. elegans expressing were imaged every 10 minutes throughout their development and computationally straightened. green marks the pharynx, red the total body.