Speakers

Title: “Unraveling the Insect Microbiome”

Abstract: Insect symbionts can be classified into obligate and secondary facultative symbionts. The primary symbionts are nutritional symbionts which reside within a specialized organ, the bacteriome. These primary symbionts (like Wigglesworthia, Buchnera etc) produce important nutrients, mainly amino acids and vitamins, to their diet-dependent hosts such as aphids, tsetse flies, ants, stinkbugs, weevils, psyllids, lice and sharpshooters. The secondary facultative symbionts can be detected in diverse cell types and organs. These symbionts can be beneficial to their hosts by providing protection against heat, parasitoids, viruses and insecticide resistance.

Gut-associated bacteria are members of this category and recent studies increasingly suggest their importance in several aspects of insect host biology and physiology including nutrition, immunity and behavior. The insect gut microbiota can also engage in opportunistically harmful interactions with the host. During the last years, and with the advent of molecular biology and next generation sequencing techniques, research on symbiosis has been rekindled with an emphasis on untangling the diversity and the functional role symbionts have on all aspects of host biology.

Title: “Genomic analysis of Mycobacterium strains highlights the potential of reverse vaccinology in aquaculture”

Abstract: Globally, aquaculture has faced serious economic problems due to bacterial, viral, and other infectious diseases of different origins. Mycobacterium species have long been recognized as a significant source of morbidity and mortality in aquaculture. Several basic aspects of mycobacterial pathobiology in aquatic animals remain poorly understood, although a number of important recent developments have been made, especially with respect to identification of novel Mycobacterium spp. infecting fishes. Currently there are no widely accepted treatments for fish mycobacteriosis. In this study, we report the isolation and characterization of two mycobacteria namely M. pseudoshottsii and M. hippocampi, from meagre and European sea bass respectively, originating from aquaculture farms in Western Greece. Reverse vaccinology was deployed to explore the antigenic diversity of the newly isolated strains. In this way, selection of candidate genes was based on a series of different in silico predictions, using publicly available or newly sequenced genomic and proteomic data. These genes were assembled by cloning in the pcDNA 3.1 eukaryotic expression vector and their immunogenicity effects were estimated in zebrafish upon vaccination. Genes associated with MHC antigen processing were analyzed by qPCR and the results revealed activated MHC-I and MHC-II pathways even during the early stage of vaccine immunization. The strongest gene target candidates will be prioritized in future vaccine development efforts to prevent future Mycobacteriosis outbreaks.

Title: “New targets and new prevention and treatment strategies against bacterial infections”

Abstract: Compounding the problem of antimicrobial resistance is the immediate threat of a reduction in the discovery and development of new antibiotics, the dangers of which have recently been made clear by the World Health Organization and other European institutions. Consequently, a perfect storm is converging with regard to bacterial infections: increasing antimicrobial resistance with a decreased new antibiotic development. In this environment, our research line has been focused on acquiring relevant knowledge in the field of microbiology and infectious diseases, in particular, i) the study of the host-bacterial interactions in vitro and in animal models, and ii) the role of bacterial outer membrane proteins in the infection process, with the aim of developing new molecules with antibacterial activity.

Title: “The use of protein crystals in Biotechnology and Pharma industry”

Abstract: Biocatalysts make use of the versatility, selectivity and specificity of enzymes to catalyze a variety of processes to produce relevant compounds under mild conditions. To extend the lifetime under extreme conditions and to increase the efficiency, enzymes are immobilized in different materials or in the form of aggregates and crystals. Cross-Linked Enzyme Crystals (CLECs), the best solution to enhance catalyst lifetime and recoverability, is having a renaissance mainly boosted by the extensive knowledge gained during the last two decades in protein crystallization and to the new used as scaffolds materials.

We have applied the knowledge acquired from crystallization in convection-free environments to produce protein crystals for biotechnological applications. In this lecture I will give a brief summary of the potential uses of protein crystals assayed in our lab including: i) CLECs for the development of enhanced-robust biosensors, ii) reinforced cross-linked enzyme crystals (rCLECs), for large scale enzymatic reactions with durable auto-supported catalysts and iii) reinforced protein crystals for controlled drug delivery systems.

Title: “Machine learning in the era of multi-omics data: Applications and perspectives”

Abstract: Advances in so-called omics technologies have revolutionized biological approaches to solving bioscience problems and led to the accumulation of big omics data, catapulting the biosciences into the era of Big Data. Learning valuable insights from large omics datasets requires the right combination of software and hardware to solve the computational problems faced by bioinformaticians. Meanwhile, machine learning has undergone a similar revolution in recent years, taking advantage of high-performance computing and large data collections. Integrating the resulting data from different branches of omics technologies and studying them in a multi-omics domain can pave the way to a better understanding of biological processes. In this talk, we will look at how machine learning has significantly improved our knowledge in biology and biomedicine by integrating genomics, transcriptomics, proteomics, metabolomics, and other omics data. We will also discuss some of the applications of artificial intelligence in omics and the challenges and prospects of machine learning as omics technologies continue to advance.

Title: “Identification of Novel Microsomal Prostaglandin E2 Type 1 (mPGES-1) Inhibitors By Conducting Structure-Based Virtual Screening”

Abstract: Prostanoid biosynthesis starts with the metabolism of arachidonic acid (AA) to prostaglandin (PG)G2 and PGH2 by cyclooxygenase (COX)-1 and COX-2. Pathway proceeds with PGE2 synthases (PGES). Those enzymes (cPGES, mPGES-1 and mPGES-2) convert PGH2 to PGE2, an inflammatory lipid mediator. Nonsteroidal anti-inflammatory drugs (NSAID) inhibit COX activity and suppress PGE2 production and many other lipid mediators such as PGI2, PGD2, and thromboxane (Tx)A2. However, these drugs are causing gastrointestinal bleeding and several cardiovascular complications. Therefore, blocking PGE2 production at a lower step of the pathway via mPGES-1 inhibition is expected to result in a safer and more promising treatment of inflammation, cancer, and cardiovascular diseases. We decided to develop reliable binding determination workflows and for that purpose we manually curated bioactivity data of 8k mPGES-1 inhibitors. We followed two parallel virtual screening campaigns with the biological evaluations of the hit compounds. Both workflows focused on screening the same million-scale in-stock compound library. The first workflow used only molecular mechanics (MM)-based approaches and the second workflow consisted of convolutional neural networks (CNN)-based protein-ligand binding mode generation approaches. Novel potent compounds were derived with prospective hit discovery approaches by utilizing both in silico and in vitro evaluations.

Title: “Presentation of new species discovered for the flora of Morocco”

Abstract: The flora of Morocco always brings new discoveries due to the climatic and topographical diversity, and the vastness of its territory. Since the publication of the last volume of the “Flore Pratique du Maroc” (Fennae et al., 2014), more than 30 new species have been described, and probably more than 50 new occurrences have been published. This confirms the need to carry out explorations in the field. During the last years, our extensive research lead us to discover some new species for science and Morocco. In this presentation, we will present the last five discovered species in south east of Morocco: Gypsophila struthium, Senna alexandrina, Centaurea peltieri, Centaurea achilleifolia and Phlomis lychnitis (Homrani and Peltier, 2020a; 2020b; Homrani and Susanna, 2021, 2022).

Keywords: Biodiversity, New species, Discovery.

Title: “Quorum sensing functioning stochasticity and quorum quenching action of natural bioactive compounds to fight against bacterial infections”

Abstract: It has been suggested that the regulation of gene expression in bacteria is only related to concerted and induced mechanisms. In recent decades, it seems evident that bacteria coordinate interactions either among themselves or with higher organisms, following intercellular communication systems often based on the expression of new genes, called quorum-sensing (QS) systems. This system regulates a number of activities in bacteria such as pathogenicity, biofilm formation, and antibiotic resistance. Indeed, QS induced participates in the formation of biofilms, which allow bacteria, in certain circumstances, to resist antibiotics. Furthermore, understanding the mechanism of QS signals could be exploited to specifically counterbalance the formation of biofilms and possibly the resistance developed by the bacteria they form. Today, several researchers have deciphered the precursors and the main molecular intermediates of QS and the exact regulation they undergo. This mechanism has directed pharmacological research on infectious diseases to develop molecules that can inhibit the generation of QS signals, interfere with their signaling pathways, and block their transport between the extra- and intracellular environment. The development of anti-QS molecules requires specific screening of several molecules of diverse chemical nature. Moreover, the screening of natural molecules extracted from medicinal plants as anti-QS therapeutic agents has two selective advantages, the phylogenetic links between the different organisms and the molecular mimicry that has been demonstrated between the QS intermediates and the secondary metabolites of medicinal plants. Indeed, recently, several studies have proven the quorum quenching (anti-QS) properties of natural molecules extracted from medicinal plants. These molecules, due to their diversity and their biochemical complexity, act in different ways against QS mediators and biofilm formation. From a multidisciplinary interface perspective, this screening can be carried out via in silico approaches by studying the molecular interactions between the active molecules and the various QS mediators.

Title: “In Silico studies of Stachys Biomolecules against associated proteins of Pseudomonas aeruginosa quorum sensing.”

Abstract: During the last years, the increasing spread of multidrug-resistant bacteria has become one of the most important public health issues. This resistance is largely due to biofilm formation and the expression of virulence factors, which are controlled mainly via a cell-cell communication mechanism called quorum sensing (QS). In the case of Pseudomonas aeruginosa (P.aeurginosa), an opportunistic Gram-negative human pathogen and one of the main causes of nosocomial infections, QS is regulated by six proteins LasR, LasI, RhlR, RhlI, PqsR and PqsA. Many plant-based compounds have demonstrated anti-infection activity. The genus Stachys has received much attention for screening its bioactive secondary metabolites from different parts of the plant. Considering the research done so far, Stachys species can be considered a favorable subject to the exploration and discovery of secondary metabolites with antimicrobial potential. In the present study, we aimed to identify Stachys biomolecules that can be considered as potential inhibitors of the six key QS proteins in P. aeruginosa, based on an in silico approach. For this purpose, 186 molecules from the Stachys database were screened against the six chosen targets. Next, molecules were selected based on binding energy and then filtered on Lipinski's rule of five parameters and ADME/T properties. The interaction of the retained biomolecules with the P. aeruginosa targets was analyzed by secondary docking. The 10 selected biomolecules are: 5-demethylnobiletin, chrysosplenetin, 3'-Methoxycalycopterin, 8-Methoxycirsilinol, Calycopterin, Casticin, 5-Hydroxyauranetin, 5,3',4'-Trihydroxy-3,6, 7,8-tetramethoxyflavone, syringic acid and vanillic acid. We suggest that the inhibitory effect of these 10 biomolecules will be tested for experimental validation against P. aeruginosa.

Keywords: Quorum sensing, P. aeruginosa, Stachys, Lipinski, ADMET, biomolecules, molecular docking.