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Meiotic recombination is initiated in diploid germline cells by the programmed introduction of hundreds of DNA double strand breaks (DSBs) along chromosomes. These DSBs are then repaired by homologous recombination, one of the outcomes being the crossovers, where homologous chromosome arms are exchanged. Meiotic crossing overs are necessary for gamete viability. Errors in meiotic crossover formation are the major source of aneuploidies leading to sterility and chromosomal diseases such as Trisomy 21. Meiotic recombination is also an important source of genetic diversity, generated through the crossovers that shuffle existing combination of alleles, but also through the unidirectional events called conversions that take place at all meiotic recombination sites. We have recently uncovered a new function of the poorly characterized mismatch repair complex, MutLbeta (Mlh1-Mlh2 in budding yeast), in meiotic recombination. We found that it interacts with recombination proteins to regulate their activity and limit the extent of genetic material exchanged between homologs…

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Cross-linking mass spectrometry (XL-MS) is increasingly used for structural characterization of multi-subunit protein complexes. Chemical cross-linking captures conformational heterogeneity, which typically results in conflicting cross-links that cannot be satisfied in a single model, making detailed modeling a challenging task. Here we introduce an automated modeling method dedicated to large protein assemblies that (i) uses a form of spatial restraints that realistically reflects the distribution of experimentally observed cross-linked distances, (ii) automatically deals with ambiguous and / or conflicting cross-links and identifies alternative conformations within a Bayesian framework, (iii) allows subunit structures to be flexible during conformational sampling. We demonstrate the power of our method by testing it on known structures and available cross-linking data. We cross-linked and modeled  the 17-subunit yeast RNA polymerase III at atomic resolution. The resulting model agrees remarkably well with recently published cryo-electron microscopy structures and provides additional insights into the polymerase structure. 

Biological systems are composed of many interacting components - in ecological communities, populations of different species. Though the first models for interacting populations date to almost a century ago, the role of species interactions in regulating the response to perturbations, and in shaping community composition, is yet not well understood. Models for ecological communities have so far concentrated on small systems. Here I show that, on the other hand, large ecological communities display simple and consistent patterns that can be understood as the result of elementary stochastic processes. Using random matrix techniques, I study how the properties of the interaction networks influence the stability of ecological communities and the persistence of the populations. I conclude with a list of challenges that need to be overcome to have a more complete understanding of statical and dynamical properties of large ecosystems.

A general understanding of the complex phenomenon of protein evolution requires the accurate description of the constraints that define the subspace of proteins with mutations that do not appreciably reduce the fitness of the organism. Such constraints can have multiple origins, and here such constrained evolutionary trajectories are represented by a Markovian process throughout a set of protein-like structures artificially constructed to be topological inter- mediates between the structure of two natural occurring proteins. The number and type of intermediate steps defines how constrained the total evolutionary process is. The Caterpillar coarse-grained protein representation allows for both quantitative protein design and folding, making it the perfect tool for constructing the evolutionary trajectories. In fact, with computer simulations it is shown that, for a large set of real protein structures, the model produces designed sequences with similar physical properties to the corresponding natural occurring sequences. Ultimately, the Caterpillar model is unique in the…