Abstract

Many insect species including mosquitoes transmit a wide range of pathogens to animals and humans, causing a variety of vector-borne diseases (VBDs). For humans, VBDs currently account for more than 17% of all infectious diseases causing more than 700,000 deaths annually. Thus, insect disease vectors (IDVs) pose a significant threat to global public and animal health and have substantial socioeconomic impacts. Although effective control of IDVs is crucial, it is also challenging.

Insects rely on their olfactory system to sense volatile chemicals that regulate crucial behaviors, including social interactions, mate and oviposition site selection and food source location. An effective and safe control method for their control involves the use of long lasting, environmentally friendly repellents and anosmia-inducing agents. These agents interfere with the olfactory capacity of blood feeding insects and reduce the frequency of their biting host organisms and transmitting pathogens to them.

Insect odor receptors (ORs) are heteromeric ligand-gated cation channels expressed in olfactory sensory neurons. Each receptor is composed of one of many variable subunits, ORx, which confer specificity to odor recognition, and an obligatory receptor subunit, ORco, which is necessary for channel formation and signal transduction. ORco is highly conserved amongst different insect orders, spanning many hundreds of millions of years of evolution. In the absence of a co-expressed ORx subunit, ORco can form, at least ex vivo, homotetrameric cation channels whose function may be activated or suppressed by synthetic ORco agonists and antagonists, respectively. Moreover, ORco antagonists have broad inhibitory activities on the majority of heteromeric ORs of a variety of insects. Given such considerations, the identification of volatile ORco antagonists that may interrupt insect–host recognition and thus reduce and prevent the spread of VBDs, is crucial.

This presentation will describe the recent development of an integrated screening platform consisting of an ex vivo guided, ligand-based in silico screening element and ex vivo and in vivo functional validation assays. This platform is employed on collections of natural volatile metabolites in conjunction with the odorant coreceptor of the African blood feeding mosquito Anopheles gambiae, AgamORco, in order to achieve an accelerated pace of discovery of ORco antagonists of natural origin. The employment of this screening platform resulted in the identification of several AgamORco antagonists that inhibit the function of most mosquito odor receptors, cause anosmia to multiple mosquito species and block their biting behaviors, thereby their capacity to transmit IVDs to animal and human hosts. Ongoing molecular modeling and molecular dynamics (MD) studies on 3D-models of AgamORco, which aim to identify antagonist-binding sites and -binding modes, as well as relevant functional correlations, will also be presented and discussed.

Biography

Dr. Kostas Iatrou, formerly Professor of Biochemistry and Molecular Biology at the Faculty of Medicine, University of Calgary, Canada (1981-2001; Adjunct Professor 2001-today) and Director of the Institute of Biology at the National Centre for Scientific Research “Demokritos” in Athens, Greece (1988-2003), is the Head of the Institute’s “Insect Molecular Genetics and Biotechnology” Group. His expertise is in insect developmental genetics, molecular biology and biotechnology.

Abstract

Biomass gasification with steam injection in a fluidized bed reactor has emerged as a promising method to improve syngas quality by increasing hydrogen production. In this work, a simplified yet comprehensive three dimensional multiphase model incorporating combustion chemistry and heat transfer was integrated into AVL FIRE CFD software through the implementation of user-defined subroutines. Biomass combustion and gasification for four different bed materials acting as catalysts to the biomass pyrolysis process with steam injection were investigated for this work. Beechwood was consistently used as the biofuel for all the experiments while varying the bed material. Four various types of bed materials (Silica sand, Olivine, Na–Y Zeolite, and ZSM-5 Zeolite) were used in the study and a constant steam injection was maintained. ZSM-5 Zeolite exhibited the highest hydrogen production under steady-state condition. The present model was validated against experimental results available in the literature for a lab-scale fluidized bed reactor. The model’s results of species concentrations of the syngas were analyzed and compared with the experimental results and found reasonable similarity.

Biography

I am Warnakulasooriya Dinoja Sammani Fernando, a final year PhD student at Swinburne University of technology in the department of mechanical engineering and product design engineering. My research areas are CFD modelling of biomass and plastic gasification to produce hydrogen energy. Further, I work on modelling of agglomeration formation in fluidized bed reactors when biomass/iron oxide is combusted. Below are the links to my publications.

Abstract

An analysis of 1200+ existing missense ACE mutations revealed that 400+ mutations are damaging and led us to hypothesize that carriers of heterozygous loss-of-function (LoF) ACE mutations (which result in low ACE levels) could be at risk for the development of late-onset Alzheimer’s disease (AD) [Danilov, 2024]. 1st stage of ACE-dependent AD project is characterization of blood ACE levels, catalytic properties and conformation  (ACE phenotyping) using a wide set of mAbs to ACE, developed in our lab. We performed already ACE phenotyping in 200+carriers of 80+ different ACE mutations and 200+controls. We found that several of relatively frequent AD-associated ACE mutations (at least 2% of population) are truly damaging and, likely, transport-deficient, with ACE levels in plasma only ~50% of controls. Some other AD-associated ACE mutations did not cause a decrease in ACE and, likely, did not affect surface ACE expression. Therefore, their mechanism of association with AD is different, likely via catalytic changes. However, both these types of ACE mutations  may result in reduced degradation of amyloid beta peptide Aβ42, an important component for amyloid deposition. Consequently, these could pose a risk factor for the development of AD. Therefore, a systematic analysis of blood ACE levels in patients with all ACE mutations has the potential to identify individuals at an increased risk of late-onset AD. Individuals with transport-deficient ACE mutations may benefit from future preventive or therapeutic interventions aiming to enhance ACE protein traffic, as we  previously demonstrated for transport-deficient ACE mutation, Q1069R [Danilov, 2010].

Biography

Sergei M. Danilov has completed his PhD at the age of 28 years from National Cardiology Research Center, Moscow, Russia and postdoctoral studies also ther. He is the Principal Investigator and Head of the laboratory of ACE biology in the Division of Pulmonary and Critical Care in the Department of Medicine in the University of Illinos at Chicago. His laboratory developed more than 40 mAbs to ACE. He has published more than 200 papers on ACE biology and immmunochemistry in reputed journals and has been serving as an editorial board member of Biomedicines.

Abstract

It is shown that the proteins folding process which depends mostly on amino acids sequence is also influenced by the environmental conditions. Water directs the process toward the construction of micelle-like form (hydrophobic core with polar surface) what can be expressed in fuzzy oil drop model (FOD) by the 3D Gauss function thus expressing the environment in form of continuum. Comparison of idealized hydrophobicity distribution (accordant with 3D Gauss function) with the observed one allows identification of local discordance in respect to micelle-like organization in form: local hydrophobicity excess suggests the place for complexation; the local hydrophobicity deficiency identifies the cavity including catalytic cavity. The membrane environment expects in opposition to water environment the hydrophobic residues to be exposed on the surface. The modification of 3D Gauss function by the presence of the opposite distribution makes the FOD-M (M-modified) applicable to any external conditions for folding process. The proposed model allows the quantitative assessment of the degree (expressed by K parameter) of opposite factors influencing the folding process. In consequence the interpretation of many local energetic minima representing different structures may be treated as the result of consensus between internal and external force field. This is why the traditional funnel model with many local minima may be treated as external force field dependent. FOD-M model is assumed to be applied for protein folding process simulation In Silico producing the structures appropriate for conditions ensuring the achievement of the biologically active structural form.

Biography

Irena Roterman-Konieczna has completed her PhD at the age of 30 years from Nicolaus Copernicus Medical Academy Krakow, postdoctoral studies from Cornell University – H.A.Scheraga Group. She was director of Bioinformatics and Telemedicne Department – Jagiellonian University – Medical College. She has published more than 140 papers (PubMed) in reputed journals and has been serving as cheif editor of the journal Bio-Algorithms and Med-Systems (2005-2020) . She has published more than 5 books – open access: Springer (https://link.springer.com/book/10.1007/978-3-031-31557-2, https://link.springer.com/book/10.1007/978-3-319-65639-7), Elsevier (https:// www.sciencedirect.com/book/9780081029817/from-globular-proteins-to-amyloids). The main interest: protein folding as the process with active participation of environment.