The SMB research group is organised in 7 research labs in the Lisbon pole in a total of 22 integrated members (11 permanent faculty; 1 MD PhD; 10 non-permanent research staff) who supervise 21 PhD students.

The SMB group leverages a suite of spectroscopic techniques, to drive research on biomolecular interactions, elucidating structural and functional relationships, advance drug discovery, and understand biomolecular dynamics and regulation. The SMB group is now able to study larger and more complex biostructures by an integrative approach using NMR, X-ray crystallography and cryo-EM.

An area of active synergized research at SMB is Glycoscience to understand mucin O-glycan biosynthesis and recognition, unravelling host-human microbiome and immune system interactions in the context of infection and cancer.

The SMB group will pursue structural and functional studies on the understanding of biological nanocages, particularly from the ferritin family proteins and encapsulins enabling the rational design of protein nanocages further assembled into functional fibers. The extracellular electron transfer pathways of electrogenic bacteria are in the frontline to develop sustainable application in the bioremediation, bioenergy and bioelectronics.

By using a combination of diverse and synergic structural and biophysical methodologies, we will study the role of liquid-liquid protein phase separation in neurodegenerative diseases and monitor conformational changes of membrane protein transporters involved in neurotransmission. Further structural studies (x-ray, cryo-EM and Time-Resolved Serial Synchrotron Crystallography) will uncover enzymatic mechanisms of complex metalloenzymes (eg CO2 reductase) for applications with environmental impact (eg CO2 reduction). Metalloenzymes involved in detoxification of copper and reactive oxygen species in pathogenic bacteria will also be studied and contribute to design new antimicrobial agents.

The MMG group comprises 6 labs (Lisbon and Porto), 24 researchers (15 permanent faculty; 1 MD PhD; 8 non-permanent) and 18 PhD students and will tackle two main topics:

1) mechanistic understanding of basic aspects of cell functioning that are globally relevant for adaptation, especially during environmental changes;

2) integrated knowledge of microbial pathogenicity and antimicrobial resistance that spans from molecular mechanisms to single cell analysis and microbial populations.

The 1st research line envisages the development of novel fermentations for health, food, and beverage sectors. Ecology and niche adaptation in the contexts of yeast domestication and food spoilage will be addressed using comparative and population genomics and the resources available at PYCC. Omics approaches will also be deployed to study the impact of HGT on the evolution of metabolism in a bee-health promoting yeast lineage.

The 2nd research line covers projects from infection biology to epidemiology and evolution of antimicrobial resistance, and the role of the microbiome in health and disease. For example, we will delineate the targetome of virulence effector proteins from important human pathogens (C. trachomatis and L. pneumophila). We will also explore the link between complex sugar importers and biofilm formation in two Gram-positive bacteria (B. subtilis and S.aureus) and will elucidate the impact, on host and interspecies interactions, of a new peptide system of S. aureus that enhances macrophage internalization in gram-negative bacteria. Besides strengthening and expanding the novel systems developed for bacterial monitoring, we plan to explore functions and microbiome interactions as a source of bioactive compounds to support the development of novel and innovative treatment approaches, or improvement of bioinoculants for sustainable plant production. Previously implemented outreach (MicroMundo@UPorto) and service (CCP) activities will be expanded.

The Disease Pathways & Biomarkers (DPB) comprises 5 Research Labs in the Lisbon and Porto poles, including 21 integrated members (15 permanent faculty; 3 MD PhD; 5 non-permanent research staff) who directly supervise 12 PhD students.

The DPB operates primarily in the UCIBIO Health program, where we aim to discover early biomarkers for chronic diseases, in close collaboration with Hospitals in Porto, Coimbra and Lisbon. Key examples are biomarkers for kidney disease (endothelial dysfunction, tubular, fibrotic & inflammatory injuries), cancer (breast, pancreas, colorectal), and neurological disorders (stroke and neurodegeneration). Using cutting-edge technologies such as multi-omics approaches, bioinformatics, genome editing (e.g. CRISPR/Cas9), and advanced imaging techniques, we also aim to decipher complex disease pathways and identify molecular targets for intervention.

The DPB activities encompass fundamental research, translational studies, and clinical applications, contributing for personalized medicine approaches, namely stroke clinical trials for new diagnostic and prognostic biomarkers Also, we will continue to develop open-source bioinformatic pipelines (github.com/comicsfct), data analysis software (sites.google.com/view/mitoneuro/software), novel disease models, and gene editing strategies, sharing them with the scientific community.

Further, DPB researchers will continue to train Master and PhD students, and contribute to the scientific and broader society via organization of scientific meetings (e.g. internationals such as mitoporto.com), workshops/courses (e.g. Computational Biosciences using HPC systems in collaboration with the national infrastructure INCD), and outreach events (e.g. disease awareness weeks).

DPB contributions will be fostered by successful and long-term international collaborations (e.g. Ana Pombo MDC Berlin; Elisa Espinet, Meritxell Rovira IRB Barcelona; Mike Murphy MRC Cambridge; Michael Duchen UCL London).

The Toxicology RG (TOXI) comprises 6 Research Labs distributed in the Lisbon and Porto poles with a total of 51 integrated members (30 permanent faculty & research staff, 13 non-permanent faculty, 8 non-permanent research staff) who directly supervise 45 PhD students, excelling in the field of Toxicology.

One of the group aims is to identify chemoresistance mechanisms and early toxicity and biomarkers in cancer survivors, particularly related to cardiotoxicity, for enhanced diagnosis and personalized interventions. Across preclinical to clinical translation, the group contributed to Alzheimer’s disease treatments targeting the BACE-1 and GSK-3β pathway.

Collaborating with the pharmaceutical industry, such as Avextra Pharma GmbH, we aim to investigate the toxicological impacts of psychedelic drugs like psilocybin, psilocin, and N,N-dimethyltryptamine, to enhance their safety profile. We also aim to explore the neurotoxicology of psychoactive substances using an Adverse Outcome Pathway-based approach on both developing and mature brains, including epigenetic signatures and changes in aging biomarkers to understand individual susceptibility and implications in neurodegenerative diseases. Additionally, we seek insights into the toxicity mechanisms of emerging drugs of abuse using new experimental models like C. elegans and zebrafish. We will delve deeper into the forensic impact of legal and illegal psychoactive substances on driving safety and causes of death, aiding in more informed court decisions. Collaborating with the Forensic Research Center of Simon Fraser University, we will expand the use of new techniques for analyzing alternative samples like bones and teeth, which are more resistant to decomposition.

In the environmental field, we focus our research on developing methods for analyzing microplastics and the enantioselective toxic impact on aquatic organisms and microorganisms and to understand the physiology of stress and disease caused by environmental stressors.

The PBMed research group comprises 5 Research Labs distributed in the Lisbon and Porto poles in a total of 25 integrated members (21 permanent faculty & research staff and 4 non-permanent research staff) who currently supervise 30 PhD students.

PBMed is dedicated to developing diagnostic and therapeutic innovative and personalised solutions to address unmet medical needs, with a particular focus on congenital disorders of glycosylation and on age-related chronic diseases.

The strategy of PBMed is threefold, aiming i) to develop diagnostic solutions for better patient stratification and therapy personalisation; ii) to explore drug repurposing and target therapies in cancer, neuroinflammation, obesity and skin ageing, applying the concept of Circular Bioeconomy in pharmacotherapy; iii) to develop advanced and innovative drug delivery systems for precision molecular biomedicine.

The pharmacological and genetic expertise and the in-depth knowledge of metabolic and signaling pathways brought together in PBMed will allow the identification and development of drugs (antibodies or small molecules) rationally designed or repurposed that can be used to improve the available disease treatments. The use of real-world data will be explored to build models for patient stratification and personalized therapeutic approaches. The technological expertise of PBMed will allow the development of the next generation of drug delivery technologies, nanodevices, gene and genome editing, antibody technology, and precision drug delivery to reach previously undruggable targets and maximize drug action with minimal adverse effects.

Special attention will be paid to societal impact and the translation of knowledge to the industry, aligning competencies with the priorities of smart specialization strategies in health, and strengthening cooperation with the biotech, diagnostic and pharma companies, patient associations, and research institutes participating in smart specialization platforms.

BENG comprises 6 Research Labs in the Lisbon pole in a total of 24 integrated members (7 permanent faculty & research staff and 17 non-permanent research staff) who supervise 38 PhD students. This group applies bioengineering principles, as well as artificial intelligence-based models, to develop and optimize bioprocesses and bio-inspired solutions to address challenges in the health and the bioeconomy.

Leveraging our unique pilot plant facilities and industrial partners, the scale-up of bioprocesses will be done to ensure cost-effective and sustainable production of biopolymers from wastes and translation to industry. Emphasis will be given to online spectroscopic tools for real-time bioprocess control. Also, BENG will develop deep hybrid modelling tools that merge first-principles models, AI and deep learning along 3 focus areas: 1) Bioprocess digital twins for industry 5.0; 2) AI for metabolic engineering; 3) In silico culture media design.

On biomanufacturing, BENG will also contribute to the development of more sustainable fermentation (ongoing Pathfinder projects) and downstream processes (ongoing FET-OPEN project) aiming at reducing the cost and environmental footprint of biologicals manufacturing.

Research also focuses on developing sensors for health and environmental applications, using biodegradable and stimuli-responsive biomaterials. Specifically, the olfaction-inspired materials and technologies from two ERC PoC grants will provide new solutions for managing bladder cancer and diagnosing Parkinson’s disease. Additionally, a high-throughput screening platform for olfactory evaluation, with implications for the fragrance industry, will be developed.

Exploration of the actinobacteria biorepository, housing over 1500 strains from the Macaronesia Atlantic ecozone, as cell factories for producing pharmaceutical compounds and biopolymers with diverse properties, will continue, thereby contributing to the growth of Blue Bioeconomy.