Aquaporins (AQPs) are a family of 13 small integral membrane proteins, whose primary function is to facilitate the passive transport of water across the plasma membrane of the cell, in response to osmotic gradients created by the active transport of solutes. These small membrane-spanning proteins assemble as homotetramers in which each monomer is composed by an extracellular and cytoplasmic vestibule connected by a central amphipathic pore region in a barrel like arrangement. [2]
These proteins are widely expressed throughout the animal and plant kingdom, being localized in the plasma membrane and in the cytoplasmic compartments, particularly in cell types that are involved in fluid transport. AQPs have been proven to play key roles in tumor biology, including histological tumor grade, proliferation, migration, angiogenesis, or tumor-associated edema, namely due to its over-expression when compared to normal tissues. Therefore, AQPs can work as potential diagnostic and therapeutic targets in anticancer treatment, since their inhibition in endothelial and tumor cells might limit tumor growth and spread. [3] Unfortunately, the hit rate for the identification of small-molecule AQP modulators appears to be very low when compared to other membrane proteins, and the few available pharmacological modulators lack specificity or show high toxicity. [1] One of the possible explanations for this low druggability is the small size of the functional AQP monomer and its small pore diameter. Nonetheless, the continuous growing of structure/function knowledge on AQPs, particularly the atomic-level geometry of specific hydrophobic and hydrophilic residues in the pore region, makes AQPs a promising therapeutic target to be used in future computational drug discovery campaigns. [2] However, in order to achieve successful results, new and innovative approaches and methods must also be developed. Consequently, we are currently developing a new computational workflow based on several distinct methods that combine innovative ligand and structure-based approaches to identify new AQP modulators. In this work, we will present the first steps of the developed protocol, focusing our studies on AQP – subtype 1.

[1] Castle, N. A. (2005). Aquaporins as targets for drug discovery. Drug Discovery Today, 10(7), 485–493.
[2] Verkman, A. S., Anderson, M. O., & Papadopoulos, M. C. (2014). Aquaporins: important but elusive drug targets. Nature Reviews Drug Discovery, 13(4), 259–277.
[3] Wang, J., Feng, L., Zhu, Z., Zheng, M., Wang, D., Chen, Z., & Sun, H. (2015). Aquaporins as diagnostic and therapeutic targets in cancer: How far we are? Journal of Translational Medicine, 13(96).

In this study, molecular topology was used to develop several discriminant equations capable of classifying compounds according to their antibacterial activity.

Topological indices were used as structural descriptors and their relation to antibacterial activity was determined by applying linear discriminant analysis (LDA) on a group of quinolones and quinolone-like compounds.

Four extra equations were constructed, named DF3, DF4, DF5 and DF6 (DF1 and DF2 were built in a previous study), all with good statistical parameters such as Fisher-Snedecor F (> 25 in all cases), Wilk’s lambda (< 0.36 in all cases) and percentage of correct classification (> 80 % in all cases), which allows a reliable extrapolation prediction of antibacterial activity in any organic compound.

The results obtained clearly reveal the high efficiency of combining molecular topology with LDA for the prediction of antibacterial activity.

Due to the current global health problem of antibiotic resistant recently announced by the World Health Organization, there is an imperious necessity of looking for new alternative antibacterial materials able to treat and impede multidrug-resistant infections which are cost-effective and non-toxic for human beings. In this regard, carbon nanofibers (CNFs) possess currently much lower cost than other carbon nanomaterials such as graphene oxide, and exhibit excellent chemical, mechanical and electric properties. Thus, here, we show the antibacterial activity of CNFs against a globally spreading multidrug-resistant pathogen, the methicillin-resistant Staphylococcus epidermidis (MRSE). This Gram-positive bacterium is becoming one of the most dangerous pathogens due to its abundance on skin. In this study, these hollow filamentous materials, in direct contact with cells showed no cytotoxicity for human keratinocyte HaCaT cells, which render them very promising for biomedical and bioengineering applications. The CNFs used in this work were characterized by Raman spectroscopy and observed by high-resolution transmission electron with energy-disperse X-ray spectroscopy.

Acetylcholinesterase (AChE) is one of the most relevant therapeutic targets for the symptomatic treatment of Alzheimer’s disease. Hence, the development of new molecules capable of inhibiting AChE activity is an effective therapeutic strategy. The incorporation of halogens (X) in drug molecules is a common way to enhance drug ADME (absorption, distribution, metabolism, and excretion) properties, often leading to increased potency. However, halogenation can also improve drug-target binding affinity due to the existence of halogen bonds (HaBs) established with the receptor. Halogen bonds (R-X...B) are noncovalent interactions between a positive region on the electrostatic potential of X, called sigma-hole, and a nucleophile, such as a lone pair of a Lewis base (B).

Since there were virtually no reports on the use of HaBs to target AChE, in this work, we searched for amino acids frequently targeted by halogen bonding (called hotspots) in the AChE binding site. For that purpose, all the compounds containing a moiety capable of halogen bonding (Ph-X, Ph = phenyl, and X=Cl, Br, I) were retrieved from the ChEMBL database and docked into the AChE binding site using AutoDock Vina XB whose scoring function takes into account the sigma-hole. Multiple X-ray structures and molecular dynamics snapshots from the target were used to account for conformational variability. By applying a geometrical criteria, we selected all halogens atoms engaged in HaBs, thus being able to identify halogen bonding hotspots on the binding pocket. These preliminary results will be the starting point for obtaining new halogenated scaffolds to target AChE, hopefully helping in the design of new and more effective AChE inhibitors.

Ancient societies first attempted to domesticate wild plants for food production, which gave rise to present-day agriculture. Nowadays, more than a third of agricultural production is lost due to abiotic or biotic stress, such as drought, salinity, pests and diseases. Current predictions indicating an expanding world population until the end of the century, one of humanity's greatest challenges should be how to feeding the world in a sustainable way, as future increases in crop yields should be achieved with fewer input of fertilizers and pesticides. These challenges have raised awareness of the importance of the plant root microbiome to improve agricultural and horticultural practices.

Plant roots are colonized by a surprising number of microorganisms, revealing in most cases an intimate symbiotic relationship which facilitates nutrient uptake and provides the host plant with higher resistance against attackers. In this context, plants can be seen as "superorganisms" that depend on their root microbiome for important functions. But the impact of plant domestication on the functional diversity and beneficial activities of this root microbiome is still largely unknown. Recent studies showed taxonomic differences in the root microbiome between wild relatives and modern cultivars, mainly in root architecture and root exudation. This leads to the hypothesis that present-day cultivars might have lost traits to recruit and activate host-specific beneficial root microbiota.

Our research project investigates tomato species and native soils in the Andes to explore the taxonomic and functional diversity of their root microbiomes. Next generation sequencing and ‘omics technologies, combined with classic microbiological techniques are being used to obtain insight in the diversity of root-associated microbial communities of tomatoes. We hypothesize that wild tomatoes grown in their native soils harbour unique and higher frequencies of beneficial root microbiota, compared to modern cultivars.

Ancient societies first attempted to domesticate wild plants for food production, which gave rise to present-day agriculture. Currently, more than a third of agricultural production is lost due to abiotic or biotic stress and future increases in crop yields should be achieved with fewer input of fertilizers and pesticides. These challenges have increased awareness of the importance of the plant root microbiome.

Plants are colonized by a surprising number of microorganisms, revealing in most cases an intimate symbiotic relationship, but the impact of plant domestication on the functional diversity and beneficial activities of this root microbiome is still largely unknown. Recent studies showed taxonomic differences in the root microbiome between wild relatives and modern cultivars, mainly in root architecture and root exudation. This leads to the hypothesis that present-day cultivars might have lost traits to recruit and activate host-specific beneficial root microbiota.

Our project investigates tomato species and native soils in the Andes to explore the taxonomic and functional diversity of their root microbiomes. Next generation sequencing and ‘omics technologies, combined with classic microbiological techniques are being used to obtain insight in the diversity of root-associated microbial communities of tomatoes. We hypothesize that wild tomatoes grown in their native soils harbor unique and higher frequencies of beneficial root microbiota, compared to modern cultivars.

During the poster sessions of the 1^st International Biotechnology Conference, we present the various research initiatives we have developed within the area of Microbial Ecology of the Universidad San Francisco de Quito (USFQ).

Microbial ecology is the branch of ecology that investigates microorganisms in their ecosystems or within natural tissues, which exhibit essential functions for all living beings on our planet. It includes the study of symbioses, biogeochemical cycles and the interaction of microbes with anthropogenic effects such as pollution and climate change.

Our research team focuses on the associations between plants or animals and their respective microorganisms, thereby integrating functional macroecology with molecular and applied microbiology.

Recent revolutions in genomics have delivered an interesting toolbox of promising techniques that can help us understand the enormous amount of data generated by translating all the genetic information.

Instead of focusing on single genes, we are now able to sequence whole genomes of millions of DNA molecules, and recently it is possible to analyse a mix of many different species altogether in one single sample.

These advances allow us to accurately study the identification of the microbial community that lives in or around multicellular organisms. In addition, in a country like Ecuador with an enormous visible MACRObiodiversity, we hypothesize that the invisible MICRObiodiversity has co-evolved to a similar magnitude or even higher.

Currently, we are developing multidisciplinary research lines that focus on functional microbiomes of emblematic species which inhabit diverse landscapes like the Andean highlands, the Amazon rainforest and soon at the Galápagos Islands. We aim to facilitate the knowledge of microbiomes in benefit of the challenges that confront our planet, for instance improving the disease resistance of crops and to identify the effects that climate change might have on the health of wild populations of migratory species like humpback whales.