- 1 Quantified us: a group-in-the-loop approach to team network reconstruction.UbiComp21 Proceedings (In review)
- 6 Ancestral and offspring nutrition interact to affect life history traits in Drosophila melanogasterProceedings of the royal society B 286:1897.https://doi.org/10.1098/rspb.2018.2778
- 7 Epidemium: A multidisciplinary community to tackle cancer using big and open dataJournal of Clinical Oncology 36:e13604-e13604.https://doi.org/10.1200/JCO.2018.36.15_suppl.e13604
- 1 A study of germ layer specification of the crustacean Parhyale hawaiensis (MCO 2015).Since the first observations of embryogenesis, the specification of cell fates, from an oocyte to a terminal cell type, has been a central question. In 1940, Waddington proposed a model named the Epigenetic Landscape in which he described the specification of cell fate as a marble rolling down a landscape shaped by different gene expression patterns. Thanks to the advances of modern omics technics, it is now possible to observe the gene landscape of cells during development. However, most studies focus on classical model organisms, or in vitro models. Here, I propose to study the specification of the different germ layers of an emerging model organism, Parhyale hawaiensis, using single cell RNA sequencing measurement of development from a single cell to the so-called germ band stage, allowing for the exploration of gene regulatory networks topologies, shifts and rearrangements along the epigenetic landscape. Finally, using a Gene Positioning System (GPS) and light sheet imaging, a 3D virtual embryo will be created where one can visualize gene expression throughout the development rendered in time and space, on a single cell resolution.
- 2 The maternal to zygotic transition of the crustacean Parhyale hawaiensis. (EMBO 2017)Here I study the germ layer specification of an emerging model organism, the crustacean Parhyale hawaiensis, by using single cell RNA sequencing to quantify the gene expression landscape of embryonic development from the single cell stage to the establishment of major body plan features. Parhyale hawaiensis possesses a well defined genome, germ layers entirely derived from a maximum of three cell progenitors, a small number of cells at gastrulation, a well defined fate map of all germ layers, ease of culture and embryo collection, and ease of cell harvesting. This approach will allow me to explore the topologies, shifts and rearrangements of gene regulatory networks along the epigenetic landscape. Further, I will analyze the changes in mRNA expression landscape post MZT, notably the order and timing of gene expression, and their association with the different germ layers.
- 3 Alien invasion in the kingdom of insects (MCO 2017).To acquire new functions, evolution often relies on the creation of new genes. Well understood mechanisms of new gene creation include duplication, local mutation, and domain rearrangements. In some cases, however, genetic material can be acquired from exogenous DNA, a phenomenon known as horizontal gene transfer (HGT). oskar is a gene found only in the insect lineage that has evolved to be absolutely necessary for germ cell formation, and thus species survival, in some clades, including the fly Drosophila. Its evolutionary history, however, remains a mystery, as no homologs appear to exist outside the insect lineage. Here we elucidate the evolutionary origins of oskar, and show that oskar likely arose through a novel gene formation history. We used numerous recently published insect genomes and transcriptomes to analyze over 100 oskar sequences. We provide strong evidence that while one of oskar’s two conserved domains, the LOTUS domain, was present in an ancestral insect genome, the second one, the OSK domain, was acquired through a horizontal domain transfer from a bacterial GDSL-like lipase. Both domains would then have fused via conversion of intervening genomic DNA from non-coding to coding sequence,creating a new unique gene, which we hypothesize would have been the ancestral oskar sequence. Finally, we show that the OSK domain is related to GDSL-like lipases from a bacteria of a clade including to the genus Wolbachia, suggesting that bacterial endosymbionts could have provided source material for the HGT event that led to the genesis of oskar.
- 4 Visualizing embryo development in Virtual Reality. (MCO 2018)Embryos come in many shapes and sizes, but in all cases, they form a three-dimensional structure. With the advent of new microscopy technology such as LightSheet, it is now possible to record the development of an embryo from all angles in high resolution, generating a 3D + time dataset. However, visualizing such datasets is usually limited by the need to create two dimensional projections on a computer screen. Thankfully, the development of consumer accessible Virtual Reality (VR) now allows researchers to “immerse” themselves in 3D or 4D data, and thus, to visualize such datasets in a three-dimensional world. Here, I present a new VR tool I developed to visualize and manipulate LightSheet microscopy datasets, along with some new insights into the development of the amphipod crustacean Paryhale hawaiensis.
- 2 Transdifferentiation prediction using gene regulatory networks and genetic algorithm & Functional co-culture of motor neuron and myotubes.Cellular reprogramming, also called transdifferentiation is the process which change the fate of a defined cell type to another one. To reprogram a cell, researcher use a cocktail of defined transcription factors that induce changes in the molecular and genetic state of the cell. However they have to start with a big number of transcription factor and then reduce it. Using a motif based prediction algorithm and graph theory as well as a genetic algorithm, we constructed the gene regulatory network and scored factors to predict the importance of each of them in the reprogramming process. Amyotrophic Lateral Sclerosis (ALS) is a motor neuron degenerative disease poorly understood. Motor neuron normally form Neuro Muscular Junction with myotube, and that junction seem to be implicated in ALS. Here we propose a new in vitro coculture system of human embryonic stem cell derived motor neuron and chicken myotubes. That system allows study of the Neuro Muscular Junction formation and might lead to a better under standing of ALS as well as drug screen. We also propose an in vivo model to study the behavior of motor neuron injected in the neural tube of a chicken embryo.
- 3 Inference of WW domain Sequence-Function relationship using noisy measurements.Protein’s function is ultimately determined by its amino-acid sequence which in turn determine its structure. The general problem of the sequence-function relationship is very complicated and some case studies that focus on a well-defined function in a small portion of the sequence space can be informative. Here, we show that using a protein display assay coupled with high-throughput sequencing, it is possible to examine quantitatively the effect of thousands of mutations around a reference sequence. This approach rely solely on the sequences-function relationship and can provide valuable insights on the mechanisms of a protein without prior structural knowledge. The ability to extract valuable knowledge in the noisy context of biological experiments is made possible thanks to new inference techniques based on Information Theory. Using a simple model that considers each amino acid as independent we demonstrate the ability to infer an energy model for the binding of the hYap65 WW domain, which recapitulates to a certain extent the thermodynamics laws of a binding event. Finally, we extended our analysis by looking at the sequence-structure relationship of two other WW domains.
- 4 Computational approaches to developmental biology.The origin and evolution of new genes is an active topic of research, relying on the taxonomical diversity now present in sequence databases. Using those databases, we described how oskar, a key determinant of germ cell determination, likely arose from a horizontal gene transfer and then described its evolution and conservation in insects. The number of ovarioles, the egg-producing unit of the insect ovary, is hypothesized to inform the individualʼs reproductive capacity. Using network biology approaches, we analyzed the effect of signaling pathway genes on the number of ovarioles and eggs laid by Drosophila melanogaster. We found putative gene modules regulating both traits and predicted novel genes affecting both phenotypes. The specification of germ layers is a central mechanism of the embryogenesis of animals, but the underlying molecular mechanisms have only been extensively studied in model organisms. Using Parhyale hawaiensis, a crustacean amphipod, I generated preliminary methods for the generation of single cell RNA sequencing of early embryogenesis, as well as recorded with light sheet microscopy the first three days of embryogenesis. The preliminary analyses of the sequencing datasets were inconclusive, but, analyzing one of the microscopy datasets, I described new preliminary cellular dynamic results. Finally, to observe and annotate 4D microscopy datasets, I developed a tool that allows the visualization of large volumetric datasets in Virtual Reality.