Periodic Reporting for period 1 - SocBehGenoPheno (Genetic basis of emergent social behaviour from genotype-phenotype mapping)
Periodo di rendicontazione: 2019-07-01 al 2021-06-30
The aim of this project is to quantify the genotype-phenotype mapping in C. elegans social behaviour using quantitative collective modelling based on high-throughput tracking data. The specific goals describe a three-stage procedure:
Goal 1: Develop a dictionary of worm behavioural states. This goal will be accomplished in two steps: I will first identify various behavioural states based on worm postures and tracking data and then quantify transitions between the different worm states within this behavioural map.
Goal 2: Build an agent-based model (ABM) and refine it to match the experimental summary statistics. This work will be also done in two steps: I will build an ABM that captures multiple behavioural worm states and subsequently parameterise and refine it to match the experimental summary statistics.
Goal 3: Derive and assess genotype-phenotype mapping by extracting a low-dimensional representation of the model. This is the most ambitious and risky goal. To achieve it, I will extract phenotypes and test their similarity among almost 200 C. elegans strains.
A major achievement so far toward Goal 2 has been to design summary statistics of the wave-front characteristics using a roughness index. Remarkably, this shows fascinating scaling behaviour, different for the mutants. Another major achievement was a new method to measure the uptake of bacteria by the worms, based on bioluminescent bacteria. This allowed to understand the differential of uptake depending on mutant and location in the wave. This was published in:
Ding SS, Romenskyy M, Sarkisyan KS, Brown AEX. Measuring Caenorhabditis elegans spatial foraging and food intake using bioluminescent bacteria. Genetics 214(3): 577-587 (2020); doi: 10.1534/genetics.119.302804.
Ongoing work is on Goals 1, 2, and 3: Regarding Goal 1, a principal-component-based analysis method was developed, capturing subtle differences in posture according to worm density and mutants. Regarding Goal 2, an agent-based model is currently refined to capture observed network structures of collective worm behaviour off food and wave propagation with different scaling behaviour on food. Key ingredients are local worm-worm alignment, oxygen sensing, and food uptake. Regarding Goal 3, the low-dimensional representation will be the wave (and network) formation. Key challenges will be separation of subtle changes in collective behaviour in different mutants, while extracting the main robust features.
Due to Covid-19 lockdowns, dissemination occurred in Year 1 mainly through seminar talks, presentation at the Quantitative Biology of C. elegans Behavior meeting in Amsterdam and lecturing on the MSc in Applied Biology and Biotechnology. The results have been also disseminated through social media, in particular using twitter account of the fellow and the project webpage.