The ICTP-ICTS Winter School on Quantitative Systems Biology is an annual program, jointly organized by the International Centre for Theoretical Sciences, Bengaluru, India, and the Abdus Salam International Centre for Theoretical Physics, Trieste, Italy. Each year, the school focuses on a specific area of quantitative systems biology, while the venue for the school alternates between Bengaluru and Trieste. The aim of these schools is to help researchers from theoretical sciences transition into life science research and for experimental biologists with quantitative backgrounds to assimilate theoretical perspectives and methodologies in their research.
The 8th edition of the School was held at ICTS between 9-20 December 2019 and was focused on the theme of ‘Morphogenesis’. Experts from across the globe working on cell and tissue morphogenesis and related topics were invited to speak and deliver lectures. Around 80 early career researchers and students, from institutes and universities both across India and abroad participated in the School.
Keeping in mind the diverse academic backgrounds of the participants, a week-long pre-school to cover basic concepts in cell and developmental biology and mathematical and physical approaches to biology was organized. Pedagogical lectures by Prof. Maithreyi Narashimha, Dr. Vijay Krishnamurthy, Prof. Vidyanand Najundiah and Dr. Fernando Casares, set the stage for the two-week long main-school.
Lectures by Prof. Maithreyi Narashimha (TIFR-Mumbai), were aimed to help the participants understand the general principles that govern the patterning of structures in living systems. They focussed on explaining how chemical and physical cues enable cells to sense their neighbourhood and moderate their behaviour, ensure correct formation of tissues, control and coordinate mechanisms related to tissue deformation and large-scale cell movements. She also provided insights into the ideas and methodologies that have helped researchers understand the process of morphogenesis over the years, and have paved the way for advanced techniques, enabling scientists to engineer tissues and grow organoids in petri-dishes.
Dr. Vijaykumar Krishnamurthy (ICTS, Bengaluru) started his session by sharing with the participants a broad view of developmental biology and morphogenetic processes, as seen from the viewpoint of a condensed-matter physicist. He then setup basic ideas in stochastic processes, chemical kinetics and random walks, as a framework to understand the reaction-diffusion and active mechanochemical patterns. He also introduced ideas from hydrodynamics and active matter as a prelude to the lectures in the main school.
Prof. Vidyanand Nanjundiah (CHG, Bengaluru) is a well-known scientist with interests in diverse subjects including developmental, evolutionary and theoretical biology. His lectures outlined the historical perspective on ‘evo-devo’ and its ongoing transition into ‘eco-evo-devo’, evolutionary origins of multicellular development and an understanding of commonly used terms such as Neo-Darwinism, plasticity, epigenetics and noise.
Dr. Fernando Casares (CABD, Sevilla) in his lectures shed light on topics such as organizational principles of development and construction of morphospace. He also touched upon problems regarding organ size control; termination and variation (relative and precision).
ICTP-ICTS Winter School- Week One
The first week kick started with lectures by Prof. Mounia Lagha (IGMM, Montpellier), who studies early transcriptional processes in the fruit flies (Drosophila melanogaster). Her lectures focused on transcription in early embryos, the crucial role of enhancers and promoters in this process, and the associated gene regulatory networks. She also gave a peek of the results obtained by her research team using imaging methodologies, and insights into transcriptional bursting and the subsequent synchrony of temporal processes in an early embryo.
Dr. Mounia Lagha (IGMM, Montpellier) works on early transcriptional processes in fruit fly embryo.Photograph copyrights: ICTS-TIFR
Prof. Tim Saunders (MBI, National University of Singapore, Singapore), uses a combination of theoretical and experimental methods to study processes in developmental biology. In his lectures, he presented models to explain the formation of morphogen gradients from a localized source, and how these provide the embryo with spatial information. He also spoke about feedback mechanisms for regulation of the morphogens and touched upon the essentials of FRAP (fluorescence recovery after photobleaching) and FCS (fluorescence correlation spectroscopy) techniques.
Prof. Tim Saunders (MBI, National University of Singapore, Singapore) combines theoretical and experimental methods to study processes in developmental biology.
Photograph copyrights: ICTS-TIFR
Regulation of shape and division in eukaryotic cells and its application to cancer research is the focus of Prof. Buzz Baum’s (Medical Research Council Laboratory for Molecular Cell Biology, UCL, London) research. In his lectures, he explained how evolution tunes the way genotypes lead to phenotypes in eukaryotic cells and presented a robust model of cellular automata showing evolution. He introduced the idea of how eukaryotic cells might have arisen from archea-bacteria, and how this can help better understand the evolution of nuclear division in eukaryotic cells. Baum also spoke about the mechanisms that disrupt normal cellular behavior and thereby give rise to cancer cells.
Prof. Guillaume Salbreux (Francis Crick Institute, London, UK) uses ideas from physics to describe biological systems at various length scales. During his lectures, he described the theory for active fluids, which serves as a continuum model for tissues. He also introduced ideas from differential geometry and a theory for the mechanics of active surfaces, which arises due to coupling between an active fluid on a thin film and the resulting deformations.
Dr. Fernando Casares’s (CABD, Sevilla) research examines the principles controlling organ size in organisms using fruit fly as the model organism. In his lectures, Dr. Casares highlighted the specific subsystems in the fruit fly, such as the wing and eye imaginal discs, where problems of robustness and relative precision can be addressed in detail. He also discussed the evolutionary perspectives in variation of organ size and its implications on our understanding of scaling of organ size.
Dr. Fernando Casares (CABD, Sevilla) examines the principle controlling organ size in organisms. Photograph copyrights: ICTS-TIFR
The first week of the School came to an end with Prof. Frank Jülicher (Max Planck Institute for the Physics of Complex Systems in Dresden, Germany) delivering the Infosys-Turing Lectures- a four-part series on active processes in cells and tissues. In these lectures, Jülicher presented models for symmetry breaking in cells by mechano-chemical coupling, leading to pattern formation and surface deformations. He spoke on phase separation in active fluids and how it can capture centrosome dynamics or model coacervates. He also introduced the vertex model that captures the dynamics of epithelial sheets, using wings of fruit flies as an example. Jülicher also spoke about morphogen gradients, using scaling arguments to show that temporal control of these can account for the growth profiles observed in the lab.
Prof. Frank Jülicher of the Max Planck Institute for the Physics of Complex Systems delivered the Infosys Turing-Lectures. Photograph copyrights: ICTS-TIFR
ICTP-ICTS Winter School- Week Two
Week two began with Prof. Karen Alim (Max Planck Institute for Complex Systems and Self-Organization, Göttingen, Germany) presenting ideas in flow networks, using statistical physics and fluid mechanics. Alim’s work examines the dynamics of fluid networks and plant growth. In her lectures, she spoke on how transport and absorption of materials occur in these networks and also derived its steady state concentration profile. She also spoke on how a network of connected tubes could be seen as a minimal model of a leaf and demonstrated the derivation of an expression for the optimal flow velocity for homogeneous absorption in a tube.
Prof. Jochen Rink (Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany) studies tissue development in planarian flatworms. In his lectures, he demonstrated using illustrations, how and why Planarians are ideal model organisms to study tissue formation. In addition, his lectures explored mechanisms of polarity at various length scales, and how long and short range order arise. He also spoke about the size variability in biological organisms, metabolic scaling laws, and how size affects the molecular mechanisms in flatworms.
Prof. Jochen Rink (Max Planck Institute for the Physics of Complex Systems) studies tissue development in flatworms. Photograph copyrights: ICTS-TIFR
A bio-physicist working on the sensory systems in plants, Dr. Yasmine Meroz (Tel Aviv University, Israel) in her lectures focussed on mechanisms about how plants detect gravity, and presented universal models for the growth and regulation of shape of plant shoot. These models have applications in sensory growth systems, including GrowBot, a project on which. Meroz’s research team is working.
Dr. Yasmine Meroz (Tel Aviv University) works on the sensory systems in plants. Photograph copyrights: ICTS-TIFR
Dr. Matteo Rauzi (University of Nice, France) were based on the dynamics of cellular rearrangement as an important driver for tissue morphogenesis. He discussed the coupling of topological re-arrangements of cells with morphogen gradients that pattern the axes in embryos of fruit flies. Emergent supracellular structures were then shown to drive tissue polarization and extension. Dr. Rauzi also discussed several experimental techniques in his lectures.
Dr. Vikas Trivedi (EMBL, Barcelona) and his research group at EMBL aim to understand the self-organization of cells, a process fundamental to metazoan development through comparative study of embryos and organoids that generate a global coordinate system de novo. In his lectures, he discussed how conserved signalling pathways in early embryos, which though limited in number, are responsible for robust formation of body axes and the emergence of axial patterns over time. He also introduced the participants to the concept of modularity in biology and how different morphological processes can result in similar geometrical results. Trivedi also addressed the difficulties one faces in imaging a beating heart in its different phases and positions and the need for developing techniques and instruments to quantify processes observed during cell morphogenesis.
Prof. Vikas Trivedi’s (EMBL, Barcelona) work focuses on the mechanism behind self-organization of cells. Photograph copyrights: ICTS-TIFR
Prof. Stefano de Talia’s (Duke University, USA) in his lectures discussed the temporal aspects of chemical and mechanical signals during early embryogenesis and tissue regeneration in fruit flies and zebrafish. He touched upon the theory of chemical waves, and its use as a medium to account for cleavage cycles in early embryogenesis. He also spoke about regeneration waves and the way in which the excitable chemical waves of ERK influence tissue growth, as a medium to model morphogenesis.
Prof. William Bialek (Princeton University, USA), is known best for his influential series of studies where he applied the principles of information theory to analyze the neural encoding of information in the nervous system. In his lectures at the School, he introduced the participants to the idea of positional information. He used ideas from statistical physics, probability and information theory to show how optimization of information passed on from primary morphogen gradients to output of gene regulatory networks lead to accurate determination of the position of a cell in the embryo.
Prof. William Bialek (Princeton University) is a well-known theoretical biophysicist. . Photograph copyrights: ICTS-TIFR
The ICTP-ICTS Winter School in Quantitative Systems Biology is a unique program that helps brige gaps between theoretical sciences and experimental sciences and like with the previous editions, this year too, the School was received very positively and with much enthusiasm by the participants. “This School is very non-conventional. It gave insights from different scientific fields and topics”, said Darshan Shah, a PhD student from the Indian Institute of Technology, Bombay. “It was a well-balanced combination of experimental and theoretical topics”, said Ajay, a PhD student at the Institute of Mathematical Sciences, Chennai. In addition to talks by experts, the School had student poster sessions, that not only enabled participants to get familiar with each other’s work, but also gave them an opportunity to present their work with the speakers. The next edition of ICTP-ICTS Winter School on Quantitative Systems Biology will be on the theme ‘Ecology’ and will be held at Trieste, Italy in November 2020.
Poster session provided participants the opportunity to interact and share their research with each other. Photograph copyrights: ICTS-TIFR
Participants interact with Prof. Antonio Celani (left), Dr. Yasmine Meroz (center) and Prof. Jochen Rink (right), during the poster session. Photograph copyrights: ICTS-TIFR
N. Aniruddha (ICTS)
Shray Chaturvedi (ICTS)
Vijaykumar Krishnamurthy (ICTS)
Aditya Singh Rajput (NCBS)