Research Projects 2019
In their application, the candidates must choose 2 of the following MAIN RESEARCH PROJECTS and 1 of the ADDITIONAL RESEARCH PROJECTS (by order of preference).
THE ON-LINE APPLICATION FORM WILL BE AVAILABLE ONLY ON THE 17th OF DECEMBER
MAIN RESEARCH PROJECTS
Research Project 1
Title: Structural studies of liquid phase proteins related to human disease
Scientific Area of PhD: Chemistry
Scholarship Type: Mixed
Summary: Protein liquid-liquid phase separation (LLPS) may lead to the formation of cellular membraneless proteinaceous organelles that constitute an effective responsive strategy for biological compartmentalization. These have been shown important for cellular homeostasis and disease, constituting a different liquid medium that recruits specific proteins and excludes others, and where particular reactions are promoted and others inhibited. In this project, using state-of-the-art NMR combined with other biophysical techniques (fluorescence microscopy, optical spectroscopies and calorimetry), we will unravel the molecular factors determining protein LLPS, and study the effects on structure and dynamics of proteins inside the liquid droplets. This will provide important information on biomolecular function and disease mechanisms, paving the way for future pharmaceutical and biotechnological applications.
Instituição de Acolhimento: Faculdade de Ciências e Tecnologia, UNL
Morada: Quinta da Torre, Departamento de Química, Faculdade de Ciências e Tecnologia, Universidade Nova de Lisboa, 2829-516 Caparica, Portugal
Orientador Científico: Eurico Cabrita, FCT-Universidade Nova de Lisboa
Co-orientador 1: Douglas Laurents, CSIC Madrid, Espanha
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Research Project 2
Title: Studying the immunomodulatory action of novel chromone-based compounds by NMR metabolomics and metabolic flux analysis
Scientific Area of PhD: Chemistry
Scholarship Type: National
Summary: This work aims at investigating the immunomodulatory action of nature-inspired chromone-based compounds, with a view to contribute for the development of novel anti-inflammatory therapies. NMR metabolomics and NMR-based stable-isotope metabolic flux analysis will be employed to assess how immune-inflammatory cells (e.g. macrophages) reprogram their metabolism and change their phenotypes upon different treatments. This approach is expected to greatly advance current understanding of chromones biological activity, as well as to open new prospects in the field of anti-inflammatory immunotherapy.
Instituição de Acolhimento: Universidade de Aveiro
Morada: Departamento de Química, CICECO, Universidade de Aveiro, Campus Universitário de Santiago, 3810-193 Aveiro, Portugal
Orientador Científico: Iola Duarte, CICECO – Aveiro Institute of Materials, Department of Chemistry, Universidade de Aveiro
Co-orientador 1:Artur Silva, QOPNA, Department of Chemistry, Universidade de Aveiro
Co-orientador 2: John Jones, Center for Neuroscience and Cell Biology (CNC), Universidade de Coimbra
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Research Project 3
Title: Dissecting the supramolecular dynamics of the virulent Tir during infection
Scientific Area of PhD: Molecular Biosciences
Scholarship Type: Mixed
Summary: The translocated intimin receptor, Tir, is essential for EHEC and EPEC virulence. Once injected into host cells, as the first step of infection, Tir goes from the cytosol into plasma membranes to attach the pathogen to the surface and hijack host cellular processes. The dynamics and structural assembly of Tir in eukaryotic cells have a huge impact on virulence, but it remains largely unexplored, in particular from a quantitative/structural point of view. The project concerns the molecular and atomic description of Tir and its self-organisation in membranes using hybrid structural approaches (NMR/SAXS).
Instituição de Acolhimento: Instituto de Tecnologia Química e Biológica António Xavier, UNL
Morada: ITQB - Instituto de Tecnologia Química e Biológica, Av. da República (EAN). Apartado 127. 2781-901 Oeiras, PORTUGAL
Orientador Científico: Tiago Neto Cordeiro, ITQB - Instituto de Tecnologia Química e Biológica
Co-orientador: Markus Weingarth, Bijvoet Center, Univ Utrecht
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Research Project 4
Title: An Ancient Iron-Sulfur Cluster Biosynthesis System
Scientific Area of PhD: Chemistry
Scholarship Type: Mixed
Summary: Pathogenic bacteria, such as Neisseria gonorrhoeae that causes the sexually transmitted disease gonorrhea, are constantly exposed to reactive oxygen species (ROS) and have developed defense mechanisms to cope with oxidative stress. Bacterial peroxidase is one of these enzymes. This enzyme catalyzes the reduction of hydrogen peroxide to water, with the required electrons being donated by small electron shuttle proteins. We intend to isolate and determine the structure of a small cytochrome c and characterize its interaction with the bacterial peroxide using different techniques (cell microscopy, RT-PCR, microcalorimetry, NMR). These results will contribute to the understanding of the involvement of Neisseria gonorrhoeae bacterial peroxidase has a first line defence mechanism against exogenously produced hydrogen peroxide in the host environment.
Instituição de Acolhimento: Faculdade de Ciências e Tecnologia, UNL
Morada: Quinta da Torre, Departamento de Química, Faculdade de Ciências e Tecnologia, Universidade Nova de Lisboa, 2829-516 Caparica, Portugal
Orientador Científico: Sofia Pauleta, FCT-Universidade Nova de Lisboa
Co-orientador 1: Lucia Banci, CERM, University of Florence
Co-orientador 2: Corinne Aubert, CNRS Marseille, France
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Research Project 5
Title: NMR-aided development of new olefin metathesis catalysts for pharmaceutical applications
Scientific Area of PhD: Chemistry
Scholarship Type: National
Summary: Homogeneous OM catalysts are powerful synthetic tools, Ru catalysts in particular due to their tolerance to functional groups, but their separation from the reaction media is difficult and hampers industrial application. New supported catalysts that combine the versatility of homogeneous catalysts with ease of separation and catalyst recyclability will be developed. NMR will be a key technique in catalysts characterization (liquid and solid state), surface characterization, catalyst active species and decomposition pathways (DNP).
Instituição de Acolhimento: Instituto Superior Técnico, Universidade de Lisboa
Morada: Departamento de Química, IST, Av. Rovisco Pais, 1, 1049-001 Lisboa, Portugal
Orientador Científico: Maria João Ferreira, Instituto Superior Técnico, Universidade de Lisboa
Co-orientador 1: Mariana Sardo, CICECO, Universidade de Aveiro
Co-orientador 2: Ana Margarida Martins, Instituto Superior Técnico, Universidade de Lisboa
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Research Project 6
Title: NMR and EPR study of the interaction of 3-hydroxy-4-pyridinone chelates with Biological Membranes
Scientific Area of PhD: Biomedical Sciences
Scholarship Type: National
Summary: Ligands of the 3-hydroxy-4-pyridinone class and their metal ion chelates find application in the fields Drug Design and Plant Nutrition. NMR and EPR will be used to gather information about their interactions with of biological membranes.The knowledge of the interactions of drugs/nutrients with biological membranes could allow for a better understanding of the mechanisms of delivery, transport, bio-distribution and retention of these substances in the organized media of cellular membrane. This understanding contributes to the discovery, design, and screening of novel therapeutic/nutrient agents.
Instituição de Acolhimento: ICBAS, Universidade do Porto
Morada: R. Jorge de Viterbo Ferreira 228, 4050-313 Porto
Orientador Científico: Maria da Conceição Rangel
Co-orientador 1: Eurico Cabrita, FCT-UNL
Co-orientador 2: Galya Ivanova, REQUIMTE-UP
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Research Project 7
Title: NMR study of low molecular weight components of Non-transferrin bound Iron
Scientific Area of PhD: Biomedical Sciences
Scholarship Type: National
Summary: All human cells require iron for survival, and its safe transport is ensured by serum transferrin. Non Transferrin Bound Iron is generally regarded as a source of oxidative stress, both in the circulating component and inside the cell. NTBI is able to circumvent the tightly regulated iron uptake system, promoting intracellular iron accumulation. We propose to apply modern NMR methodologies to study the low molecular weight component of NTBI in the blood serum of hereditary hemochromatosis and diabetes patients. EPR spectroscopy will also be employed and LC-MS, which has proved useful in the speciation of iron citrate complexes, will be used as a complementary methodology. We also propose to apply NMR methodologies to study protein paramagnetic metal ion centers to study the interaction of HSA with iron.
Instituição de Acolhimento: ICBAS, Universidade do Porto
Morada: R. Jorge de Viterbo Ferreira 228, 4050-313 Porto
Orientador Científico: Maria da Conceição Rangel
Co-orientador 1: Anjos Macedo, FCT-UNL
Co-orientador 2: André Neto da Silva, REQUIMTE-UP
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Research Project 8
Title: The role of conformational changes and protein dynamics of a hub protein in the infection cycle of the Influenza virus studied by in-cell NMR.
Scientific Area of PhD: Chemistry
Scholarship Type: Mixed
Summary: Influenza epidemics and pandemics are constant threats to human health and recent emergence of influenza A H5N1 and H1N1 strains has heightened these concerns. Rapid emergence of drug-resistant viral mutations has limited the use of current medicines in the market like the neuraminidase (NA) inhibitors and rendered the matrix protein 2 (M2) blockers ineffective. Therefore, there is an urgent need of novel anti-influenza drugs directed to alternative biological targets. In order to better understand the central role of one of the main viral proteins in viral proliferation, and following in vitro NMR and computational work being carried out in the laboratory, in this project in-cell NMR will be used to study the role of conformational changes and protein dynamics in the multiple interactions of this hub protein with host proteins of the infected cells.
Instituição de Acolhimento: Universidade de Coimbra (UC)
Morada: R. Larga, 3004-535 Coimbra
Supervisor: Rui M. M. Brito (Departamento de Química, Universidade de Coimbra)
Co-Supervisor: Lucia Banci (Magnetic Resonance Center – CERM, University of Florence, Italy)
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ADDITIONAL RESEARCH PROJECTS
Additional Research Project 1
Title: Probing the nano-structuring of ionic liquid based fluids using 129Xe NMR spectroscopy: towards structure-properties relationships.
Scientific Area of PhD: Chemistry
Scholarship Type: National
Summary: The complex nanostructure of ionic liquid based fluids will be studied using 129Xe NMR spectroscopy. 129Xe chemical shifts are highly sensitive to molecular medium making xenon an excellent NMR probe. Fluids with potential theranostic value will be studied, such as nanoemulsions for medical applications, seeking to establish the relation between molecular structure, organization and the properties of the fluid. Molecular Dynamics simulations will provide molecular level interpretation of the results. Other spectroscopic, thermodynamic and rheological properties will also be addressed.
Instituição de Acolhimento: Instituto Superior Técnico, Universidade de Lisboa
Morada: IST, Av. Rovisco Pais, 1, 1049-001 Lisboa, Portugal
Orientador Científico: Eduardo Filipe, CQE, IST
Co-orientador 1: José Ascenso, CQE,IST
Co-orientador 2: Ana Sofia Ferreira, FCT-UNL
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Additional Research Project 2
Title: Exploring the molecular bases of ‘unnatural’ reactivity of engineered cytochormes c
Scientific Area of PhD: Biomolecular Sciences
Scholarship Type: Mixed
Summary: Heme proteins in general and cytochromes c in particular play key roles in numerous processes essential for life. In addition to their unquestionable biological role, it has recently emerged that they can be tuned to perform reactions not found in nature. Biomolecular NMR spectroscopy is uniquely suited to investigate the structural and dynamic factors underpinning these ‘unnatural’ reactions, providing guidance for the rational design of efficient bio-based catalysts.
Instituição de Acolhimento: Instituto de Tecnologia Química e Biológica António Xavier, UNL
Morada: ITQB - Instituto de Tecnologia Química e Biológica, Av. da República (EAN). Apartado 127. 2781-901 Oeiras, PORTUGAL
Orientador Científico: Ricardo O. Louro, ITQB-NOVA
Co-orientador 1: TBA, CERM
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Additional Research Project 3
Title: Structural characterization of natural products from microalgae with anti-tumour activity
Scientific Area of PhD: Chemistry
Scholarship Type: National
Summary: Cancer is a global health problem causing approximately 7.9 million deaths each year, 70% of which in the developing world. Research carried out over the years has identified numerous natural compounds that due to its low toxicity and potential anticancer activity could be used for prevention and combat of cancer. New therapies using natural compounds or their derivatives should be developed to replace highly toxic drugs and help to increase the patients' quality of life. Microalgae appear to be an excellent under-exploited source of novel compounds displaying bioactivity against human cancer cells. The aim of this work is to find and characterize microalgal-derived compounds with low toxicity and anticancer activity against the most common types of cancer, with a focus on those striking developing countries (lung, stomach, breast, liver and cervical). Taking advantage of the large live collection of microalgae at the University of Coimbra (ACOI), multi-nuclear and multidimensional NMR will be used to characterize the compounds present in extracts of microalgae cultures with the most promising anti-tumor activity.
Instituição de Acolhimento: Universidade de Coimbra (UC)
Morada: R. Larga, 3004-535 Coimbra
Supervisor: Rui M. M. Brito (Departamento de Química, Universidade de Coimbra)
Co-supervisor 1: Eurico Cabrita (FCT-UNL)
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Additional Research Project 4
Title: Fe/S Cluster Biosynthesis System
Scientific Area of PhD: Chemistry
Scholarship Type: Mixed
Summary: Strict anaerobic bacteria present in their genome a cluster of genes that have been proposed to be involved in Iron-Sulfur cluster biosynthesis, with no resemblance to other prokaryotic system but instead are homologous to the eukaryotic ones.
In eukaryotes, these systems are involved in various severe diseases and there is an urge to understand the mechanism of action of these proteins/enzymes.
The homologous prokaryotic proteins will be biochemical and structurally characterized using different techniques and, the network of interactions will be identified and characterized (cell microscopy, RT-PCR, microcalorimetry, NMR).
Instituição de Acolhimento: Faculdade de Ciências e Tecnologia, UNL
Morada: Quinta da Torre, Departamento de Química, Faculdade de Ciências e Tecnologia, Universidade Nova de Lisboa, 2829-516 Caparica, Portugal
Supervisor: Sofia R. Pauleta, UCIBIO, FCT-UNL
Co-supervisor 1: Lucia Banci, CERM, University of Firenze, Italy
Co-supervisor 2: Corinne Aubert, CNRS Marseille, France
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