Organismal Systems Biology Lab

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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.

We use 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.

We currently focus on the nutritional control of growth and aging, and on body size homeostasis.

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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.

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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?

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 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 study if and 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.

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Individuals of C. elegans growing in arrayed of micro chambers.

 

Team

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.

[CV]

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Klement Stojanovski

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.

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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.

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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.

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Ioana Gheorghe

MSc 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.

Alumni

Artur Luzgin (internship)
Franziska Schmid (MSc)
Aaditya Saxena (BSc)
Stefano von Wyttenbach (BSc)
Julie Perey (BSc)

 

 
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Benjamin Towbin

 

 Growth  and size control

2021, bioRxiv

Benjamin D. Towbin, Helge Grosshans

2018, Cell reports

Yael Korem Kohanim, Dikla Levi, Ghil Jona, Benjamin D Towbin, Anat Bren, Uri Alon

2017, Worm

Janna Hastings, [..], Benjamin Towbin, [..],  Olivia Casanueva

2017, Nature Communications

Benjamin D Towbin, Yael Korem, Anat Bren, Shany Doron, Rotem Sorek, Uri Alon

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!

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.

Undergraduates looking for training opportunities: Please get in touch by email!

 

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.

 
 
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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.

Get in Touch

Prof. Benjamin Towbin
Institute of Cell Biology
Baltzerstrasse 4
CH-3012 Bern
Switzerland

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