Mechanics, geometry and topology of chromosomes and nuclei

During cell division, eukaryote chromosomes transform between a somewhat open interphase and somewhat closed metaphase conformation. I will discuss our group's work on studies of the mechanics of both these states of the genome.  I aim to discuss the role (and underlying mechanism) of SMC complexes in the folding, compaction, and topological organization of metaphase chromosomes, and also to describe how epigenetic marks appear to play a key role in controlling nuclear mechanics and topology.

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Modelling and predicting antigen presentation with Restricted Boltzmann Machines

Immune recognition of infected and malignant cells requires presentation on their surface of antigens (i.e. short peptides) by human leukocyte antigen class I (HLA-I) proteins, which are coded by one of the most polymorphic alleles in the human genome. The identification of clinically relevant, tumour-specific neoantigens (mutated antigens) is currently a highly sought-after goal in designing novel cancer immunotherapeutic strategies. Algorithms aimed at predicting peptide presentation by HLA-I proteins are therefore valuable tools to accelerate the validation of putative neoantigens. To tackle this problem, we resort to a framework of inference from aminoacid sequences based on Restricted Boltzmann Machines, probabilistic graphical models characterized by a layer of ‘feature’ variables. This approach ensures efficient prediction of what antigens can be presented along with their HLA-I binding specificity; furthermore, it can be used to study in a model-guided way the effect of mutations on antigen presentation.

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The origin and evolution of maize in the American Southwest

The origin of maize (Zea mays ssp. mays) in the US Southwest remains contentious, with conflicting archaeological data supporting either coastal or highland routes of diffusion of maize into the US.Furthermore, the genetics of adaptation to the new environmental and cultural context of the Southwest is largely uncharacterized. To address these issues, we compared nuclear DNA from 32 archaeological maizesamples spanning 6000 years of evolution to modern landraces from across Mexico. We found that the initial diffusion of maize into the Southwest at about 4000 years ago likely occurred along a highland route, followedby gene flow from a lowland coastal maize beginning at least 2000 years ago. Our population genetic analysis also enabled us to differentiate selection during domestication for adaptation to the novel climatic andcultural environment of the Southwest, identifying adaptation loci relevant to drought tolerance and sugar content. 

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Evolution of neuroendocrine axis in Vertebrates: impact of genome duplications

Neuroendocrine axes, composed by brain neurohormones, pituitary hormones and peripheral gland hormones, regulate major physiological functions and key-steps of life cycles in Vertebrates. We investigate how whole genome duplication events (WGD) that occurred at the basis of the vertebrate lineage (“1R and 2R” for 1rst and 2nd Rounds of WGD) and at the basis of the teleost lineage (“3R” for 3rd Round of WGD) have impacted the molecular and functional evolution of neuroendocrine axes and their roles in the control of life cycles. Model fish species investigated are chosen for their phylogenetical, ecological, socio-economical relevance and the complexity of their life cycle. 

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L’intégrité scientifique, de la responsabilité des chercheurs à celle des établissements

Je présenterai les transformations actuelles des structures en faveur de l’intégrité scientifique en France et dans le monde et je passerai en revue différentes facettes de l’intégrité scientifique, de la réflexion méthodologique aux règles de promotion et de recrutement, en passant par le soin que l’on doit porter collectivement aux données et l’incitation à la science ouverte.

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Autocatalytic networks toward Darwinian evolution

How did evolution emerge in physical-chemical systems during the origin of life? Reproduction requires autocatalysis, but evolution further requires a diversity of autocatalytic systems. In a first study, we found universal stoichiometric criteria to recognize autocatalysis in reaction networks. This analysis unifies our view of self-reproductionin already known systems and indicates that there may exist many others. In a second study, we experimentally measured the dynamics of thousands of autocatalytic RNA reaction networks. The resulting landscape reveals trade-offs between the Darwinian properties of variation and selection in self-reproducing systems. Finally, I will discuss how Darwinian evolution may ultimately be implemented in RNA recombination networks. Bibliography [1] Ameta, S., Arsène, S., Foulon, S., Saudemont, B., Clifton, B. E., Griffiths, A. D., & Nghe, P. (2021). Darwinian properties and theirtrade-offs in autocatalytic RNA reaction networks, Nature Communications (2021, in press) [2] Blokhuis, A., Lacoste, D., & Nghe, P., Universal motifs and the diversity of autocatalytic systems. Proceedings of the National Academyof Sciences, 117(41), 25230-25236…

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Multi-species annotation of transcriptome and chromatin structure in domesticated animals

Comparative genomics studies are central in identifying the coding and non-coding elements associated with complex traits, and the functional annotation of genomes is a critical step to decipher the genotype-to-phenotype relationships in livestock animals. As part of the Functional Annotation of Animal Genomes (FAANG) action, the FR-AgENCODE project aimed to create reference functional maps of domesticated animals by profiling the landscape of transcription (RNA-seq), chromatin accessibility (ATAC-seq) and conformation (Hi-C) in species representing ruminants (cattle, goat), monogastrics (pig) and birds (chicken), using three target samples related to metabolism (liver) and immunity (CD4+ and CD8+ T cells). RNA-seq assays considerably extended the available catalog of annotated transcripts and identified differentially expressed genes with unknown function, including new syntenic lncRNAs. ATAC-seq highlighted an enrichment for transcription factor binding sites in differentially accessible regions of the chromatin. Comparative analyses revealed a core set of conserved regulatory regions across species. Topologically associating domains (TADs) and epigenetic…

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