Five UCIBIO researchers have been awarded a contract in the 2020 Individual Scientific Employment Stimulus Competition (CEEC), which is the third edition of this call promoted by the Fundação para a Ciência e a Tecnologia (FCT) for doctoral researchers in all scientific areas.
Aldino Viegas and Filipa Marcelo, both in the category of Assistant Researcher, and Helena Coelho in the category of Junior Researcher, are from the (Bio)molecular Structure and Interactions by NMR Lab, led by Eurico Cabrita, professor at FCT NOVA. Sérgio Sousa in the category of Assistant Researcher leads the BioMolecular Simulations Lab at UCIBIO-UPorto, and Ana Luísa Maulvault, in the category of Junior researcher, is from the BioTox Lab, led by Mário Diniz, professor at FCT-NOVA.
The results announced by FCT indicate that 3,648 applications were evaluated by 25 international panels, of which 1,675 obtained a minimum grade to be eligible for financing. The 300 applications selected for contract correspond to 18% of the eligible applications.
Aldino Viegas’s project, NETfix (Molecular basis for ligand recognition of the human norepinephrine transporter), aims to develop a nuclear magnetic resonance (NMR) approach to study the Norepinephrine (NE) Transporter (NET), specifically it’s binding and transport mechanism. NET plays an essential role in the nervous system and its dysregulation is associated with cardiovascular diseases (CVDs), making this transporter a key pharmacologic target. NMR spectroscopy is a leading structural technique to characterize protein structure, function and interactions and, complemented by state-of-the-art molecular biology, computational and biophysical techniques can provide structural, biochemical and biophysical atomic-level details and an unprecedent mechanistic understanding of NET transport function and interactions. Aldino Viegas explains that “the goal is to develop a protocol that allows to find and characterize possible positive allosteric binding sites that can be used to discover and optimize compounds with activity for therapeutic use. The expected results will provide valuable information for early stage drug development for CVDs, thus representing a new therapeutic paradigm with a potentially significant socioeconomic impact. The proposed plan will also foster the development of new methodologies in the field of membrane protein (MP) expression and purification, combining molecular biology and the use of nanodiscs, aiming at NMR studies. Besides, it will constitute a further step to attain and consolidate my scientific independence and a leading position in the area of structural and functional studies of MPs in Portugal.”
Filipa Marcelo has been awarded the CEEC position with the project “Glycan Toolbox: From structure to function towards the development of glycan-based therapies”. Filipa Marcelo explains that “cancer is still a major cause of death, especially in cases of metastasizing or advanced stages, where the available cancer therapies (chemo- and immunotherapy) are poorly successful and generally unsatisfying. Hence, there is an unmet need for new therapies. In this context, this project aims to contribute for the design and development of novel anti-cancer therapies (glycan-based drugs and alternative immunotherapies) by targeting the abnormal glycome signature, common to all tumours and especially expressed in metastatic cancer”. Filipa Marcelo’s application presents a modern line of research in glycosciences, aiming at decoding, at the highest resolution as possible, how the tumour-glycome is created by specific enzymes and how it is read and translated by proteins, enrolled in immune modulation. The project synergistically combines high-resolution nuclear magnetic resonance methodologies with molecular modelling protocols, molecular biology and chemoenzymatic synthesis. Finally, her project will provide major breakthroughs in Life sciences with prime impact in chemistry and biology and strong implications in immunology, specifically contributing to rationally design inhibitors to block tumour growth and to develop new immunotherapeutic approaches to prevent and reduce metastasis.
The project that Helena Coelho will develop on her CEEC position is “Picturing pathogen infection: A structure-functional approach to interrogate host-glycans/Salmonella crosstalk”. The non-typhoidal Salmonella bloodstream infections affect 3.4 million people, and cause over 600.000 deaths annually, mostly in Africa. It is one of only two causes of child mortality (along with AIDS) that result in a higher rate of death today than in 1990. Furthermore, in the last few decades have witnessed the emergence of highly virulent and antibiotic-resistant Salmonella enterica strains, causing greater morbidity and mortality in humans. Helena Coelho said that “in this perspective, this project is focused on understanding how proteins present on Salmonella enterica recognize the glycans of the human host, with major goal to develop strategies to probe and eventually tune host-pathogen interactions against Salmonella infections. A multidisciplinary and integrative chemical biology strategy, combining glycan microarrays, bioinformatics, molecular biology, nuclear magnetic resonance spectroscopy, and cellular adhesion/invasion studies, will be employed, benefiting by the support of three UCIBIO research groups: the GlycoLab-Functional Glycobiology (Angelina Palma), (Bio)molecular Structure & Interactions by NMR Lab (Filipa Marcelo), and Infection Biology Lab (Jaime Mota). Ultimately, this project will create a strong and well-defined structural-functional approach, which can be extended, in a general manner, to other host-glycans/pathogens interactions”.
Sérgio Sousa’s project, entitled “Development of Biocatalysts for Industrial Applications: From plastic degradation to the Pharmaceutical chemistry”, will focus on the development and application of computational chemistry methods to understand the way how enzymes catalyze specific reactions with high efficiency and selectivity. “These methods will take advantage of quantum mechanics and high-performance computing to simulate the activity of different enzymes with potential industrial application as biocatalysts in waste management (degradation of plastic waste), and in the pharmaceutical, chemical and food production industries. The purpose is to increase their efficiency and stability through the rational introduction of specific mutations to make them potent biocatalysts more-optimally tuned for an industrial setting. These improved enzymes are expected to constitute a more sustainable and greener alternative than the current options in use in the industry, as enzymes are biodegradable and non-toxic catalysts and are able to work at lower temperatures and with non-toxic solvents. In addition, the computational methods developed will also find application in a wide range of problems dealing with the enzymatic activity, which includes the study of many enzymes of therapeutic importance”, explained Sérgio Sousa
Ana Maulvault has been awarded a CEEC position to develop the project “Farmed fish immune responses and potential eco-innovative solutions towards adaptation to the new challenges posed by climate change in Mediterranean aquaculture”. Aquaculture presently represents half of the overall seafood production, and its contribution is expected to further increase in the future, as a way to fight hunger and undernourishment of a growing world population. However, its expansion faces several challenges, like: 1) disease outbreaks (bacterial, virus, fungus or parasites) that cause massive animal mortalities and great economical losses; and 2) climate change effects that are expected to worsen in the future, on one hand, potentially favouring the growth, virulence and dispersion of microorganisms responsible for disease outbreaks, and, on the other hand, diminishing the physiological resilience of hosts. “Hence, this project aims to unravel the interactive effects of climate change-related stressors (warming coupled with heat waves and hypoxia) on the physiological and immune response mechanisms of farmed marine fish exposed to bacterial diseases. The project also aims to deliver eco-innovative adaptive solutions based on the development of tailor-made functional feeds to improve farmed fish health in tomorrow’s ocean and avoid great economic losses caused by bacterial disease outbreaks. The innovative scientific outcomes of this project will contribute to raise public awareness and engage seafood producers and stakeholders in the common goal of adapting and overcoming the challenges posed by climate change”, said Ana Maulvault.
Get to know more about the five UCIBIO awardees
Aldino Viegas is a researcher at the UCIBIO-NOVA, at Eurico Cabrita’s lab. His main research field is Biomolecular Nuclear Magnetic Resonance and his research interests have been focused on structural biology, particularly on the structural determination of proteins and small molecules, protein folding and function and intermolecular interactions. A. Viegas obtained his Ph.D. in Structural Biochemistry in 2012 (NOVA School of Sciences and Technology, UNOVA Lisboa, and, in 2013 he attained a postdoctoral position in Germany (Heinrich-Heine-Universität Düsseldorf) to study the structure and function of membrane proteins by NMR. In 2014, he was awarded a Marie Skłodowska-Curie Individual Fellowship to elucidate the molecular details underlying the interaction of the epidermal growth factor receptor (EGFR). In 2017, he returned to Portugal focusing his work in the integration of NMR with other structural biology techniques to study the effect of charged metabolites in protein-ligand interactions and protein folding and stability.
Filipa Marcelo is a Research Assistant Professor at UCIBIO-FCT NOVA since December 2016. Filipa Marcelo graduated in Chemistry from Faculdade de Ciências da Universidade de Lisboa in 2003 and obtained the PhD in Organic Chemistry in 2009 doing a joint PhD at the Universidade de Lisboa and Université Pierre et Marie Currie Paris VI in the field of carbohydrate chemistry. In 2009, she moved to Dr. J. Jiménez-Barbero’s group at Centro Investigaciones Biológicas (CSIC/Madrid) for a post-doctoral experience, where she exploited NMR to unveil molecular recognition events in Glycosciences. In 2012 she joined the research lab of Eurico Cabrita at UCIBIO-FCT NOVA with a grant from Portuguese Foundation FCT. Since January 2017, she has an independent line of research applied to structural glycosciences. She has authored of 49 original research articles, reviews, and book chapters with a more than 975 citations (h-index 17) and main coordinator of distinct ongoing projects (PTDC/BIA-MIB/31028/2017, IF/00780/2015) and research networks (COST CA18132, scientific representative of Grant Holder) in glycosciences field. She currently supervises 1 Post-doc, 3 PhD students and 2 MSc students and she has completed the supervision of 1 PhD, 3 MSc students and 7 Research trainees.
Helena Coelho graduated in Biochemistry (2011) and held her master’s degree in Biotechnology (2013) at the NOVA School of Science and Technology (FCT NOVA). After, she moved as Marie-Sklodowska-Curie fellow to Spain, through a joint PhD degree between University of the Basque Country (UPV/EHU), Spain and FCT-NOVA, Portugal, on the topic of “NMR and molecular recognition of carbohydrate-protein interactions”. She finished her PhD on March 2019. Currently, Helena Coelho is a junior post-doctoral researcher of the project entitled “Advances in MUC1 Glycan Cancer Antigens: From structure to function in the fight against cancer”, PI Filipa Marcelo, on the (Bio)molecular Structure & Interactions by NMR Lab at UCIBIO led by Eurico Cabrita.
Sérgio F. Sousa is a computational chemist specialized in computational enzymatic catalysis and computational drug discovery. He presently leads the Biomolecular Simulations lab (BioSIM, www.biosim.pt) at UCIBIO – FMUP (www.biosim.pt).
Ana Maulvault is a marine biologist (University of Algarve), with a PhD degree in Environmental Sciences and Sustainability Studies (Nova University of Lisbon). Currently, she is a researcher at UCIBIO and the Portuguese Institute for the Sea and Atmosphere (IPMA, I.P.), and collaborator at the Marine and Environmental Sciences Centre (MARE). Her research work has mostly focused on the potential interactions between environmental contaminants and climate change-related stressors in marine ecosystems, addressing the impacts from both the animal (physiology and ecotoxicology) and human perspectives (seafood safety and sustainable production).