Quantitative biology of chromosome dynamics during gametogenesis

Meiosis is the specialized type of cell division in which a diploid progenitor cell undergoes two reductional divisions, namely meiosis I and meiosis II, to produce haploid gametes. Meiosis, also called gametogenesis, is essential for promoting the genetic diversity necessary for generating new allelic combinations. The critical stage for safeguarding genetic diversity is the recombination between homologous chromosomes during meiotic prophase. Homologous chromosome search is facilitated by nuclear movements that are driven by cytoskeleton forces. Actin and dynein are two of the most evolutionary widespread motors for generating forces to move the nucleus. Nuclear movements are transmitted to the chromosomes by the formation of the telomere bouquet, a conserved chromosomal configuration in which the telomeres cluster together at specific regions of the nuclear envelope, often close to the centrosome. Even though defective telomere formation leads to serious problems in gamete production and viability, there has been little research into the molecular basis of bouquet formation and disassembly. For example, how the start and end of the telomere bouquet stage is established, the duration of chromosomal movements, and whether the telomeric movements are stochastic or predictable are not known.

To understand the nature of chromosome dynamics during gametogenesis, we develop new tools for unsupervised time series segmentation and clustering, spectral evaluation, motif discovery, and causality network discovery in the fission yeast Schizosaccharomyces pombe, one of the model systems in which chromosome movements during the telomere bouquet stage have been best explored. For example, we have designed the interactive web application ChroMo to obtain more detailed information on meiosis prophase in fission yeast and clearly differentiate phenotypes that are not differentiable by other methods. Other interest in the lab is the development of quantitative approaches to understanding the chromosome dynamics of other fundamental processes in gametogenesis, such as telomere bouquet formation or chromosome-mediated spindle formation during reductional cell divisions.

Research lines:

-Telomeres in meiosis

– Modelling the behaviour of chromosome dynamics and their possible microvariations during meiotic prophase as a result of mutations or physico-chemical stress

-Quantitative approaches to understand the dynamics of self-assembled spindles

– Computational algorithms applied to cell biology: deep and machine learning tools to identify chromosome movements patterns

Para explorar las funciones del bouquet de telómeros, utilizamos una combinación de enfoques experimentales que incluyen técnicas genéticas, bioquímicas y análisis de imagen in vivo.