Research Projects 2018

In their application the candidates must choose 2 of the following Research Projects (by order of preference)

Research Project 1

Title: Metabolomics of an endocrine-related breast cancer mouse model to study cancer progression and therapy resistance: identification of novel diagnostic and prognosis markers and translation to the human disease

PhD degree: Chemistry

Scholarship type: National

Summary:  Breast cancer (BC) is the deadliest form of cancer in women. Endocrine-related BC relies on steroid hormones, which activate intracellular receptors and stimulate tumor growth. These hormone-dependent (HD) tumors are treated with antagonist therapies aimed at such receptors, but 50% of subjects develop resistance and the disease progresses to incurable stages. This project aims at identifying the tumor metabolic profiles of i) progression (hormone treatment) and ii) regression (antagonist treatment), in a mouse BC model. Tumor samples of HD and HI response obtained from mice treated with agonist or antagonist agents, will be characterized by NMR metabolomics. The results will unveil the metabolic effects accompanying tumor progression, regression, and therapy resistance. 

Home Institution: Universidade de Aveiro

Address: Departamento de Chemistry, CICECO, Universidade de Aveiro, Campus Universitário de Santiago, 3810-193 Aveiro, Portugal

Scientific Supervisor: Ana Gil, CICECO, Universidade de Aveiro

Co-supervisor 1: Luisa Helguero, Instituto de Biomedicina (iBiMED), Departamento de Ciências Médicas, Universidade de Aveiro

Co-supervisor 2: Manolis Matzapetakis, Instituto de Tecnologia Chemistry e Biológica António Xavier, UNL 

In collaboration with Claudia Lanari, Instituto de Biología y Medicina Experimental, Consejo National de Investigaciones Científicas y Técnicas (IByME-CONICET), Argentina

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Research Project 2

Title: Studying the immunomodulatory action of novel chromone-based compounds by NMR metabolomics and metabolic flux analysis

PhD degree: Chemistry

Scholarship type: National

Summary: This work aims at investigating the immunomodulatory action of nature-inspired chromone-based compounds on human macrophages, 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 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.

Home Institution: Universidade de Aveiro

Address: Departamento de Chemistry, CICECO, Universidade de Aveiro, Campus Universitário de Santiago, 3810-193 Aveiro, Portugal

Scientific Supervisor:  Iola Duarte, CICECO – Aveiro Institute of Materials, Department of Chemistry, Universidade de Aveiro

Co-supervisor 1: Artur Silva, QOPNA, Department of Chemistry, Universidade de Aveiro

Co-supervisor 2: John Jones, Center for Neuroscience and Cell Biology (CNC), Universidade de Coimbra

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Research Project 3

Title: Study of Zeolite Acid Properties by Solid-State NMR 

PhD degree: Chemistry

Scholarship type: National

Summary: The wealth of site-selective information on the pore structure of zeolites obtained by spectroscopic techniques is often hampered by the lack of easy-to-control (post)-synthetic routes. In this PhD project, several high and low silica zeolites with distinct surface properties, namely acid type and strength, will be prepared and investigated through multinuclear 1D and 2D solid-state NMR, DNP surface-enhanced SSNMR and computer modeling. Phosphorous containing probes (TMPO) will be used to achieve a complete characterization of zeolites Brønsted and Lewis acidity.

Home Institution: Universidade de Aveiro

Address: Departamento de Chemistry, CICECO, Universidade de Aveiro, Campus Universitário de Santiago, 3810-193 Aveiro, Portugal

Scientific Supervisor:  Luís Mafra, CICECO – Instituto de Materiais de Aveiro, Universidade de Aveiro.

Co-supervisor 1: João Rocha, CICECO – Instituto de Materiais de Aveiro, Universidade de Aveiro.

Co-supervisor 2: Carlos Geraldes, Centro de Neurociências e Biologia Celular, Universidade de Coimbra.

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Research Project 4

Tittle: Scavenging toxic intracellular free heme using the human heme-binding protein p22HBP

PhD degree: Chemistry

Scholarship type: Mixed

Summary: Using the unique characteristics of the human heme binding protein p22HBP we aim to develop a method for the removal of toxic free heme from cells and biofluids and eventually from blood and blood products. The protein p22HBP is unique in that it binds heme tightly using an hydrophobic patch, however, although the protein has been fully characterised by NMR, the key interactions that lead to tight heme binding (Kd nM) are not completely understood. Therefore we will initially determine the key residues for p22HBP heme binding and then develop non-binding versions of the protein via site-specific mutagenesis in order to promote heme binding followed by its subsequent release. Using the inherent paramagnetism of the heme group we will use residual dipolar couplings and pseudocontact shifts in conjunction with standard NMR structural methods to characterise these proteins in Portugal and at CERM (Florence).

Home Institution: Universidade de Aveiro

Address: Departamento de Chemistry, CICECO, Universidade de Aveiro, Campus Universitário de Santiago, 3810-193 Aveiro, Portugal

Scientific Supervisor:  Brian Goodfellow, CICECO and iBiMED, Department of Chemistry, University of Aveiro.

Co-supervisor 1: Mario Piccioli, Center for Magnetic Resonance, University of Florence, Italy.

Co-supervisor 2: Anjos Macedo, Faculdade de Ciências e Tecnologia, UNL

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Research Project 5

Tittle: Structural determination of pre-miR 149 – G4 ligand – Nucleolin complex

PhD degree: Biomedicina

Scholarship type: National

Summary: Nucleolin (NCL) is a nucleocytoplasmic protein involved in the synthesis and maturation of ribossomes. NCL is overexpressed on cancer cells and therefore a potential strategic target for cancer diagnosis and therapy. NCL interacts with G-quadruplex (G4) structures through two domains, RBD 1 and 2, both containing aproximatelly 71 to 76 amino acid residues. NCL. The main objective of this PhD proposal is to understand the molecular determinants of NCL/G4 interaction. This will be achieved in several tasks that encompass the stabilization of the pre-miR-G4 structure, the NMR determination of its solution structure, and by a thorough NMR study of the molecular determinants of NCL/pre-miR-G4 recognition. Our final aim is to explore the use of NCL as a G4 transporter to use in cancer therapy.

Home Institution: Universidade da Beira Interior

Address: Centro de Investigação em Ciências da Saúde, Universidade da Beira Interior, Av. Infante D. Henrique, 6200-506 Covilhã, Portugal

Scientific Supervisor: Carla Cruz, Universidade da Beira Interior

Co-supervisor:  Eurico Cabrita, FCT-Universidade Nova de Lisboa

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Research Project 6

Tittle: Supra-molecular organisation of Tir virulence factor

PhD degree: 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).

Home Institution: Instituto de Tecnologia Chemistry e Biológica António Xavier, UNL

Address: ITQB - Instituto de Tecnologia Chemistry e Biológica, Av. da República (EAN). Apartado 127. 2781-901 Oeiras, PORTUGAL

Scientific Supervisor: Tiago Neto Cordeiro, ITQB - Instituto de Tecnologia Chemistry e Biológica

Co-supervisor:  Markus Weingarth, Bijvoet Center, Univ Utrecht

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Research Project 7

Tittle: Study of NMR superparamagnetic relaxation effects in magnetic ionic liquids

PhD degree: Physics

Scholarship type: Mixed

Summary: Magnetic ionic liquids combine the interesting properties of ionic liquids together with a superparamagnetic response under the application of an external magnetic field. The origin of this superparamagnetic effect is still to be explained. We aim at characterizing a set of imidazolium and cholinium based magnetic ionic liquid systems by employing different proton NMR techniques to investigate the molecular dynamics through relaxometry, diffusometry and viscometry studies. We aim at understanding the origin of these superparamagnetic effects at a fundamental level.

Home Institution: Instituto Superior Técnico, Universidade de Lisboa

Address: Centro de Física e Engenharia de Materiais Avançados Departamento de Física, IST, Av. Rovisco Pais, 1, 1049-001 Lisboa, Portugal

Scientific Supervisor: Pedro José Oliveira Sebastião, Instituto Superior Técnico

Co-supervisor 1: Eurico Cabrita, Faculdade de Ciências e Tecnologia, UNL

Co-supervisor 2: Teo Parella, Universidade Autónoma de Barcelona

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Research Project 8

Tittle: An Ancient Iron-Sulfur Cluster Biosynthesis System

PhD degree: 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).

Home Institution: Faculdade de Ciências e Tecnologia, UNL

Address: Quinta da Torre, Departamento de Chemistry, Faculdade de Ciências e Tecnologia, Universidade Nova de Lisboa, 2829-516 Caparica, Portugal

Scientific Supervisor: Sofia Pauleta, FCT-Universidade Nova de Lisboa

Co-supervisor 1:  Lucia Banci, CERM, University of Florence

Co-supervisor 2: Corinne Aubert, CNRS Marseille, France

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Research Project 9

Title: Structural insights into recognition and signaling of the Siglec-9 and -15 immunomodulatory receptors

PhD degree: Chemistry

Scholarship type: Mixed

Summary:  A hallmark of cancer is the presence of heavily sialylated cell-surface glycans. These glycans bind to the immune cells, through siglec lectin members, namely Siglec-9 and 15, actively contributing to tumour growth and immune invasion. This PhD research proposal is centred on the application of NMR methods, in combination with biochemical, biophysical and computational protocols to obtain structural, dynamics and mechanistic insights of Siglec-9 and 15 complexed with tumour and normal sialic-containing structures. The results will strongly contribute to the rational design of strategies to selective modulate siglec-9 and -15 immune responses in cancer.

Home Institution: Faculdade de Ciências e Tecnologia, UNL

Address: Quinta da Torre, Departamento de Chemistry, Faculdade de Ciências e Tecnologia, Universidade Nova de Lisboa, 2829-516 Caparica, Portugal

Scientific Supervisor: Filipa Marcelo, FCT-Universidade Nova de Lisboa

Co-supervisor: Alexandre Bonvin, Bijvoet Center, Univ Utrecht

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Research Project 10

Title: NMR-aided development of new olefin metathesis catalysts for pharmaceutical applications

PhD degree: 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).

Home Institution: Instituto Superior Técnico, Universidade de Lisboa

Address: Departamento de Química, IST, Av. Rovisco Pais, 1, 1049-001 Lisboa, Portugal

Scientific Supervisor: Maria João Ferreira, Instituto Superior Técnico, Universidade de Lisboa

Co-supervisor 1: Mariana Sardo, CICECO, Universidade de Aveiro

Co-supervisor 2: Maria João Ferreira, Instituto Superior Técnico, Universidade de Lisboa

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