Experimental Bioinformatics Laboratory (EBL)

Background

The Experimental Bioinformatics Lab (EBL) is dedicated to give technical and scientific support for the bioinformatics research groups for the experimental validation of their results. To this end, the EBL provides a fully equipped laboratory along with guidance and mentoring where required by the technicians, students and post-docs from the research groups. The diversity of projects pursued in the lab requires a good organisation and a great adaptability to provide the best environment for every single experiment.

Research projects

The main lines of research for each group currently requiring experimental work are the following:

Molecular Modeling and Bioinformatics (MMB)

Development of experimental pipelines at the molecular and genome-wide levels that are used to design integrative models to predict nucleosome positioning and chromatin higher structural organization as a function of cell activity, DNA damage and methylation pattern.
Synthesis and characterization (structural and functional) of nucleic acids for the refinement of Parmbsc2 Force field parameters
Development of Lipid Nano Particles to deliver Nucleic acids therapies to the cells of interest.

Structural Bioinformatics and Network Biology (SBNB)

Test and validation of compounds able to inactive key pathways known to be involved in complex diseases. Some preliminary experiments are currently performed to design a new type of drugs (RIPTAC) able to specifically eliminate a target cell.
Clarity project: Informaticians from the SBNB will use biological data to identify the perturbation signature caused by the Respiratory syncytial virus (RSV) and design small molecules capable of reverting the signature. These compounds will then be tested at the EBL in lung cell lines to confirm their effect.

Biomedical Genomics

Processing of human samples from cancer patients and healthy individuals (blood, buccal & nasal swabs, biopsies from various tissues), from human derived organoids and from mouse model tissues: PBMC isolation and preservation, DNA and RNA extractions, WGS, and staining for FACS experiments.
Preparation of libraries to perform duplex sequencing allowing the identification of very rare mutations in normal tissues to detect positive selection to discern the underlying mutational signatures, and to explore the natural saturation mutagenesis (PROMINENT - Cancer Grand Challenge and DISCERN).
Setting up of protocols to perform single cells omics (RNA and ATAC seq).
Collaborative efforts with other institutes and hospitals.

Comparative Genomics

One of the main projects performed at the EBL requires evolving yeast strains in the presence of antifungal drugs followed by whole genome sequencing to understand the mechanisms of drug resistance acquisition and the mechanisms leading to pathogenicity. The ultimate aim is the discovery of new strategies to prevent the acquisition of drug resistance in pathogenic strain such as Candida albicans or Candida auris.
Others projects study the microbiome diversity and the effect of carcinogens such as tobacco, alcohol etc on the microbiome. These projects involve DNA extraction to sequence and characterize the microbiome.

Genome data science

Researchers from the Genome data science lab perform synthetic lethality screens to identify new interactions between DNA repair pathways to help understand tumor evolution. This requires mainly cell culture work and DNA and RNA extraction for sequencing.

Techniques implemented in the EBL

Despite the specificity of each project from each group, techniques and equipment can be shared, and to facilitate our day to day work the lab is organized in subareas specifically designed to support large-scale experiments in genomics, molecular biology, nucleic acid chemistry, protein biochemistry and cell culture (mammalian, bacteria and yeast). Here is a list of the main techniques that are implemented in the lab:

Molecular Biology