Sex chromosomes often show extensive areas of suppressed recombination and cytological differentiation, a well-documented phenomenon in animals and plants. Lack of recombination is expected to limit the efficacy of natural selection, leading to degeneration in gene content. Similarly, fungal mating-type chromosomes, which are responsible for controlling compatibility during mating, can display patterns of suppressed recombination encompassing up to 90% of the chromosome length. The mechanisms responsible for lack of recombination and consequent degeneration remain unclear. Here, I propose to use comparative genomics to investigate the patterns and underlying mechanisms involved in recombination suppression and genomic degeneration in Microbotryum, a model fungal system with a range of dimorphic mating-type chromosomes. I will complement the currently available high-quality genome assemblies for twenty species in the genus with three outgroups, which will allow to polarize all genomic data. I will then use the genomic dataset to: 1) test hypotheses on the origin of recombination suppression in fungal mating-type chromosomes; 2) study the evolution of non-recombining regions in fungal mating-type chromosomes, e.g., their size and age, and the existence of evolutionary strata; and 3) study the patterns and mechanisms of genomic degeneration in non-recombining regions, namely non-synonymous substitution accumulation, transposable elements, disrupted genes, and non-optimal codon usage. Results will not only shed light on the origins and consequences of suppressed recombination and genome degradation in fungal mating-type chromosomes, but will also yield unprecedented insights into the dynamics of sexual reproduction in eukaryotes and contribute for a unified view of the evolution of dimorphic chromosomes.

In the course of the ERC Advanced Grant TERNANOMED, we have discovered that the linkage of squalene (a natural lipid) to many drugs, confers to the resulting bioconjugates the remarkable property to self-assemble as nanoparticles, due to the folded molecular conformation of squalene. This approach is unique and has never been used before. The so called "squalenoylation" technology may be considered as a generic platform to construct nanomedicines with high drug loading and targeted drug release triggered by the spacer between the drug and the squalene moiety. Remarkably, it was shown that these nanomedicines were more efficient and less toxic than the parent drugs. The gemcitabine-squalene (Gem-SQ) nanomedicine, our first candidate for further pharmaceutical developments, was shown not only to display an impressive anticancer activity in experimental tumors but also to overcome drug resistance, thus addressing a major challenge in tumor therapy. These pre-clinical data deserve further development towards translation into the clinic for the treatment of the pancreatic cancer, a devastating disease. However, the squalenic acid (SQCO2H), the chemical template essential for the synthesis of the Gem-SQ bioconjugate, is currently obtained through the Van Tamelen reaction which cannot be employed for the preparation of a clinical sample of Gem-SQ, because of the use of CrO3 (a toxic compound) and the poor yield of the reaction. Therefore, the synthesis of SQCO2H represents a lock for further clinical development of our Gem-SQ nanomedicine. The goals of the present proposal are : (i) to perform the total synthesis of SQCO2H through a new « green » chemistry way (which represents in itself a real innovation) allowing (ii) further regulatory acceptable preparation of Gem-SQ nanoparticles. Incidentally, the total synthesis of SQCO2H will avoid environmental concern due to excessive shark hunting and represents by itself some economical value as excipient for the cosmetics.

The early developmental period is very sensitive to disturbances. Parents are known to shape the early environment of their offspring through physiological and behavioural modifications. In this project, I am going to investigate what are the short- and long-term consequences of different family scenarios in development and fitness. For that, I will consider female promiscuity as a modifier of the early environment because (a) promiscuous females are more exploratory, more active, and thus, less nest-attending, and (b) males paired with promiscuous females decrease their paternal input. Therefore, offspring raised under such conditions might reach independence with a compromised body condition, decreasing their chances to survive until reproductive age. Moreover, I will explore whether females are able to compensate for the losses of paternal effort by increasing their own breeding effort, or whether chicks can compensate for the reductions in parental support. For that I will use two approaches: an empirical study with spotless starlings where I will focus on both the short- and long-term effects of promiscuity for fitness of mothers and offspring (survival and reproduction), and a comparative analysis where I will investigate the short-term effects of different breeding systems on the fitness of females and offspring. Both approaches will be integrated following a causal framework.

GenoSpec” aims at understanding the genomic processes underlying host adaptations of the ants-specific fungi from the species complex Ophiocordyceps unilateralis sensu lato by using a population genomics approach. This knowledge will contribute to the understanding of adaptive evolution, which is a major topic in evolutionary biology, and has potential applications in the development of fungal biological control agents against insect pests. Strains of O. unilateralis specific to three different ant species will be isolated from Thailand and their genomes will be sequenced, to identify the genomic changes involved in adaptation, e.g., the genes with signatures of positive selection or specific to particular hosts. Various sampling sites will allow inferences on the recent demographic history that could blur the footprint of positive selection. Dr. Noppol Kobmoo will bring his knowledge and skill on these particular fungi to enrich the expertise and the panel of biological models of the host institution (ESE laboratory, Université Paris-Sud, FRANCE) while gaining new expertise on population genetics at a genomic level. This project will start a fruitful collaboration between the host institution and BIOTEC (THAILAND) where the Fellow will return permanently after the project.

Eukaryotic algae evolutionary history is still fairly unknown. Thanks to state-of-the-art evolutionary models, next-gen sequencing and high computational capabilities, we are going to shed some light on the matter. Corallinales (red algae) and Dasycladales (green algae) are two extant living groups of calcareous algae with a rich fossil record (~140 and ~500 myr respectively). The lack of sufficient molecular data for these groups makes impossible to use such species in eukaryotic phylogeny and dating studies. This project has been planed to cover 2 objectives or evolutionary questions: The 1st objective aims 1) to generate de novo transcriptomic data for about 10 species corresponding to different Corallinales and Dasycladales lineages in order to perform phylogenomic analyses with 2 established datasets (one of 200 nuclear-coding plastid markers, and the other with 258 non-plastid genes) and the broadest possible eukaryotic taxonomic sampling; and 2) to perform molecular clock analyses using known fossil calibrations and hence provide robust divergence times for the whole eukaryotic tree but focusing on primary and secondary plastid endosymbiotic acquisitions. For both post- phylogenomic analyses (dating and divergence steps), already established collaborations will ensure proper method implementation. Using the results from the first objective, the 2nd one aims 1) to track history of plastid evolution (plastid-based dataset) comparing it with deep eukaryotic speciation events (non-plastid marker tree); and 2) to estimate diversification rates in distinct photosynthetic lineages in order to find if rate shifts correlate among them. AlgDates will allow us to establish the order, timing and correlation of events in such deep evolutionary transitions, but the knowledge acquired during this project will also provide information regarding reef formation and evolution, which can be useful when addressing or predicting calcareous ecosystem adaptations to climate change.