Phenogenomics
Phenogenomics enables biomedical scientists to take full advantage of rodent models that are genetically modified in the most optimal way possible. It is a partner in the concerted effort of generating new mouse models and to provide through comprehensive and standardized testing procedures, phenotypic annotations for these mutants as well as to ensure their open spread and secure archiving. The range of services offered on a cost-recovery basis by this occupation makes local and international research communities accessible to excess capacity.
The power and versatility of genetic tools accessible in the laboratory mouse make it the major experimental model for studying the role of mammalian gene in vivo and modeling human disease traits. Large scale random mutagenesis, either gene-driven or phenotype-driven, productive, medicine should identify new clinically relevant phenotypes and their associated genes. For such efforts to be productive, proper tools for clinical evaluation in mice need to be developed, as well as the infrastructure to archive and distribute this rapidly expanding mutant method to the community. With integrated, multidisciplinary programs, all the potential of the mouse in molecular medicine will be exploited.
Centre of Phenogenomics
Centre EPFL specialist an experimentation animal et alternatives, on contribute à la recherche best by supporting the scientific community through customized works and advice.
Through commitment, professionalism, and good team spirit, we work for the animal welfare of the laboratory mammals in accordance with laws and ethics.
The Centre for Phenogenomics is an important research infrastructure lined up at the Institute of Molecular Genetics, Prague. The CCP is unique regarding linked genetic engineering in mice and rats with systemic phenotyping, which includes specific imaging techniques, metabolomics, and complete analysis of data, SPF animal facilities, cryopreservation and record, a PDX platform, and preclinical services-all located on one BIOCEV campus site. Biomedical and biotechnological research area is especially of importance due to the specialized infrastructure and skillfulness concentration.
This service employs the generation of mutant rodent models through cutting-area technologies like zygote electroporation and DNA microinjection and the employment of CRISPR/Cas targeting devices. Other services include the injections of targeted ES cell lines to generate chimeric mice, archiving of mice, recovery of live mice from cryopreserved embryos and sperm, and weather sperm viability analysis.
Chemogenomic development
Developmental Phenogenomics biology has only recently looked to mechanisms that produce change within a species. Meeting this difficult question can shed light onto dysmorphology. It is also the central piece of development consisting of evolvability. Here we review our work on the developmental factor of shape and size variation in the vertebrate craniofacial complex. We then go on to present analyses of collective cross-founder strains and crosses, mouse mutants, and human cranial and facial morphometric work to show that mammalian skull variation probably lies along axes of covariation.
Such axes reflect modifications of fundamental developmental strategies, including chondrocranial or brain growth, outgrowth of facial prominences, and the allometric influence of general cranial growth. Such findings of pivotal developmental processes represent an important first step toward deconstructing the complex developmental genetic determinants of phenotypic variation. From such a position, complementary approaches are necessary to bridge the gap.
One is to develop a process for quantitative integration across forms of the genotype‐phenotype map. We outline our efforts toward these objectives of Phenogenomics and how these approaches can illuminate our views into the developmental bases of phenotypic variation within the vertebrate craniofacial complex.
Genome-genetic screens
Genome-wide genetic screens are unparallelly devices linking genes to bacterial phenotypes. It has the simplicity that a mutant causes a change in bacterial behavior; this strength is also its weakness. Biology is difficult with an almost infinite number of genetic backgrounds, gain- and loss-of-function changes, and combinations thereof, conferring single or many phenotypes. This genetic and phenotypic diversity of many bacterial species which have naturally been developed over decades is now more comfortably accessible.
Phenogenomics can enumerate thousands of bacteria individually by whole-genome sequencing and phenotypic profiling. Just like forward genetic screens, genotypes can be linked to phenotypes to uncover molecular networks basics of bacterial function. This step is relatively routine in mutant screens, though still the bottleneck in genome-wide related studies; these run by iteratively probing the connection of each genotype with a particular phenotype.
Due to such limitations as epistasis, linkage disequilibrium, population relation, etc., the power of this approach is limited and, in general, it captures only a small part of the underlying biology or in other words, the extensive genetic diversity of naturally occurring samples may be too difficult to interpret. Gene functions
It applied the strategy to Mycobacterium abscesses, notoriously hard to treat but not yet well understood pathogen causing increasingly more respiratory infections across the world. Our goal, initially, was to phenotype hundreds of clinical isolates from the respiratory study of patients suffering from M. abscesses lung disease. We aimed for in vitro and in vivo phenotypes, comeback bacterial infection, and treatment.
OD measurements
Phenogenomics have conducted serial OD measurements under various growth conditions as well as standard MIC assessment of some basic bacterial and drug response traits. We continued with the next step of mycobacterial infection, namely macrophage infection. We abstained from creating high-level macrophage infection assays, but instead created a high-content screen for THP-1 cells. We spent months of work and many unsuccessful work to reliably stain M. abscesses and almost abandoned this form.
Mycobacterial signal
We wanted to tag Phenogenomics only a few hundred M. abscesses with a fluorophore and subsequently hundreds of clinical isolates-and we got the important mycobacterial signal for imaging. We isolated and analyzed thousands of single cells and bacteria much less time-consuming and needed very high resolution for downstream analysis. As a last but not least point, an in vivo test for assessing bacterial virulence and potentially host responses should be included in our multi-dimensional phenotyping approach.
Functional screening
In other words, we attempted to lift the current genotype-phenotype inference from the simple association-that is, the GWAS-to the multi-modal approach to assess molecular networks’ basic phenotypic diversity. We should not fear conceptualizing Phenogenomics analyses as a magic potion but as a strategy that we, and rightfully others, will continue to develop toward better molecular consideration of bacterial behaviors.