During the project we will explore open questions in the field of physical oceanography of the Adriatic Sea.

2015-2019.

2015-2019

Croatia-Slovenia cooperation in science and technology, 2016-2017, PI S. Frka Milosavljević

2012-2016, PI (Croatia) D. Lyons, collaborator: T. Mišić Radić

2015-2016

2014-2017

Identification and functional characterization of (eco)toxicologically relevant polyspecific membrane transport proteins in zebrafish (Danio rerio)

                                                                                                                                                                                                                                                                                                                             A coordinated system of transport proteins, channels, receptors and enzymes act as cellular gatekeepers to foreign molecules, critically determining the so-called ADME-Tox (Absorption, Distribution, Metabolism, Excretion – toxicity) properties of a molecule. The polyspecific uptake and efflux transmembrane proteins are essential components of this complex cellular defense and detoxification/xenobiotic processing machinery in mammals, highly important and widely recognized in the context of pharmacology and human toxicology. However, they are scarcely investigated in non-mammalian species, and are not adequately addressed in the field of environmental toxicology. Consequently, the major goal of the proposed project is identification and detailed functional characterization of novel, (eco)toxicologically relevant uptake and efflux transport proteins that are not addressed so far in the context of environmental toxicology nor in non-mammalian species in general. Our research will be focused on selected polyspecific uptake transport proteins from the SLC21 and SLC22 (Solute Carriers) families, efflux transporters from the MATE (Multidrug and Toxic Extrusion) family, and finally, on the RLIP76 as the most recently discovered stress-responsive, multi-functional membrane protein. We will use zebrafish (Danio rerio) as a highly relevant vertebrate research model. Our methodological approach will be based on several subsequent research phases: phylogenetic and gene expression analyses; transfection studies in appropriate heterologous expression system(s); transport-activity assays; analyses of the transport mechanism and structural properties; high-throughput-screening for the identification of interactors of selected transporters among environmental contaminants; and finally, in vivo evaluation of the (eco)toxicological relevance of selected transporters using the zebrafish functional genomics tools.

The majority of studies in aquatic microbial ecology focus on the separate segments of aquatic ecosystem. Our project proposes comprehensive study of bacterial community within water column, sediment and fish as indicator of the aquatic environmental health status and its potential implications to human health.

Aquatic ecosystems throughout the world are exposed to an increasing pressure from various anthropogenic sources that release large variety of potentially harmful synthetic organic contaminants, including pharmaceutically active compounds. Most of the environmental studies of pharmaceuticals are focused mainly on the determination of parent compounds and encompass only one environmental compartment. Such simplified approach often underestimates the ecotoxicological relevance of a contaminant class, either by neglecting the contribution of its transformation products or by overlooking some critical mechanisms that may pose a threat to the environmental safety and human health. As opposed to that, this project aims at demonstrating the importance of the comprehensive assessment of aquatic contaminants, based on the study of two important groups of pharmaceuticals, macrolide antibiotics (MAs) and opioid analgesics (OAs), by including their main transformation products (TPs) and addressing the issue of physico-chemical partitioning in the exposure assessment. 

The extensive use of antibiotics for human, veterinary and agricultural purposes results in their continuous release into the environment. There is a widespread concern that this environmental pollution contributes to the increasingly problematic development of antibiotic resistance genes and bacteria, which reduce the therapeutical effectiveness of antibiotics. Many studies have shown that the elimination of antibiotics in conventional wastewater treatment plants (WWTPs) is poor simply because these units have not been designed to remove such compounds. Consequently, WWTPs are considered as one of the main ˝hotspots˝ for the release of antibiotics into the aquatic environment. As the maximum allowable concentrations of antibiotics in environmental waters are not regulated yet, scientists are concerned about negative effects of these compounds on ecosystems and public health. Therefore, in order to reduce the prevalence and dispersion of antibiotics from WWTPs, it is imperative to better understand the mechanisms relevant for their removal within WWTPs.