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

Research Project 1

Title: Metal based anticancer drug interactions with cellular components  

PhD degree: Chemistry

Scholarship type: National

Summary: This project will study how conventional and potential new metal-based anticancer drugs interact with DNA and glutathione, to assess drug mechanisms and capture processes (and subsequent bioavailability reduction) respectively. It will run together with an ongoing metabolomics project on the testing of Pt/Pd drugs on osteosarcoma cells. Conventional 1D/2D NMR and saturation-transfer experiments (polynucleotides) will be used (based on 1H, 13C, 15N and 195Pt nuclei), along with other biophysical techniques.

Home Institution: Universidade de Aveiro

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

Scientific Supervisor: Ana Gil, CICECO, Universidade de Aveiro

Co-supervisor: Helena Santos, Instituto de Tecnologia Química e Biológica, UNL

Research Project 2

Title: Exploring protein-protein and protein-RNA interactions to discover new drug candidates against Influenza virus

PhD Degree: 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 the concern. Rapid emergence of drug-resistant viral mutations has limited the use of neuraminidase (NA) inhibitors and rendered the matrix protein 2 (M2) blockers ineffective. Therefore, there is urgent need of novel anti-influenza drugs. In this project we will use approaches combining high resolution solution NMR and computational methodologies to characterize protein-protein and protein-RNA interactions and to prioritize new compounds with therapeutic potential. 

Home Institution: Universidade de Coimbra

Address: Departamento de Química, Universidade de Coimbra, Rua Larga, 3004-535 Coimbra, Portugal

Scientific Supervisor: Rui M. M. Brito, Universiade de Coimbra

Co-Supervisor: Alexandre Bonvin, Bijvoet Center, Univ Utrecht, and Irina Moreira, CNC, Coimbra

Research Project 3

Title: High resolution NMR studies of Atypia of Undetermined Significance (AUS) or Follicular Lesion of Undetermined Significance (FLUS) in human thyroid cytological samples

PhD Degree: Chemistry

Scholarship Type: National

Summary: High-resolution magic angle spinning (HR-MAS) NMR spectroscopy is the only non-invasive technique capable of measuring metabolite arrays within intact tissues. Different metabolite profiles of malignant tissues to either healthy tissues or benign growths is currently being explored as a diagnostic tool for thyroid cancer. In collaboration with physicians from the University of Porto, the aim of this study is to perform HR-MAS of cytological samples, obtained by fine-needle aspiration (FNA) from thyroid nodules with the cytological diagnosis of Atypia of Undetermined Significance (AUS) or Follicular Lesion of Undetermined Significance (FLUS) and its correlation with histopathology and spectral analysis of corresponding surgical tissues, to evaluate the ability of HR-MAS to discriminate benign from malign nodules. 

Home Institution: Universidade de Coimbra

Address: Departamento de Química, Universidade de Coimbra, Rua Larga, 3004-535 Coimbra, Portugal

Scientific Supervisor: John G. Jones, Universidade de Coimbra

Co-Supervisor: Brian Goodfellow, Universidade de Aveiro

Research Project 4

Title: Understanding the structure of surface species in heterogeneous catalysts using solid-state NMR

PhD Degree: Chemsitry

Scholarship Type: Nacional

Summary: Solid-state NMR is a powerful technique to probe the local structure of surface species in crystalline/amorphous materials. This project aims at applying advanced NMR and computational techniques to characterize such species in catalysts anchored to the surface of either inorganic or inorganic-organic hybrid materials. Sensitivity enhancement methods (isotope labeling and DNP-NMR) will be employed to unveil unprecedented details of surface interactions and reaction mechanisms.

Home Institution: Instituto Superior Técnico, Universidade de Lisboa

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

Scientific Supervisor: Maria João Gomes Ferreira – Centro de Química Estrutural, Instituto Superior Técnico

Co-Supervisor: Mariana Sardo – CICECO, Universidade de Aveiro, Ana Margarida Martins - CQE/IST

Research Project 5

Title: How does an emerging human pathogen wage the battle for iron with its host?

PhD Degree: Molecular Biosciences

Scholarship type: Mixed

Summary: Iron is an essential element for life and elaborate metabolic strategies evolved to circumvent its low bioavailability near neutral pH. However, many aspects of its uptake, storage and mobilization remain unexplored both in eukaryotic and prokaryotic cells. (Paramagnetic) NMR spectroscopy is uniquely suited to explore the biomolecular interactions that sustain the iron trafficking pathways as well as to follow the redox and spin state transitions that underpin its correct biological handling.

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

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

Scientific Supervisor: Ricardo Louro, Instituto de Tecnologia Química e Biológica António Xavier, UNL

Co-Supervisor: Mario Piccioli, CERM, University of Florence

Research Project 6

Title: NMR investigation of soluble Guanilate Cyclase

PhD Degree: Molecular Biosciences

Scholarship type: National

Summary: We want to understand the allosteric regulation of the human, soluble Guanylate Cyclase (sGC) which is the target of several drugs that treat heart failure. We will study each individual domain and how they interact with each other to understand how NO and various available drugs activate the production of cGMP. Structural NMR, relaxation, protein-protein and protein-ligand interactions will be studied by many different NMR and other biophysical techniques.

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

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

Scientific Supervisor: Manolis Matzapetakis, Instituto de Tecnologia Química e Biológica António Xavier, UNL

Co-Supervisor: Brian Goodfellow, Universidade de Aveiro 

Research Project 7

Title: Iron-sulfur Proteins Involved in Cell Division of Anaerobic Bacteria

PhD Degree: Chemistry

Scholarship type: Mixed

Summary:  The ORP complex, composed by three proteins containing iron-sulfur clusters, was identified as playing a role in the cell division of anaerobic bacteria. This protein complex is conserved among strict anaerobic organisms, including pathogenic bacteria, but specially in sulfate reducing bacteria.The Orange Protein (ORP) was firstly identified in cell extracts by its orange color, and recently shown to be part of a larger protein complex with other proteins containing iron-sulfur clusters and harboring domains with ATPase activity. The proteins composing the ORP complex will be characterized individually using biochemical techniques and structurally by NMR. In addition, the interaction between these protein will be assessed using biophysical techniques, such as ITC, and the hypothesis for their involvement in a new pathway of iron-sulfur biosynthesis will be explored using this techniques to determined how the iron-sulfur cluster is transferred.

Home Institution: Faculdade de Ciências e Tecnologia, UNL

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

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

Co-Supervisor: Lucia Banci, CERM, University of Florence

Research Project 8

Title: Ultra-high resolution structure determination of cobalt-substituted human carbonic anhydrase 2- inhibitor complexes

PhD Degree: Chemistry

Scholarship type: Mixed

Summary: We will measure the EPR and paramagnetic NMR of Co(II)-substituted human carbonic anhydrase 2 (HCA2) bound to different inhibitors to relate the changes in the experimentally-observed spectra to large ligand induced electronic changes in the Co(II) coordination sphere. Conversely the ligand positioning will be reconstructed by interpreting the experiments with high-level theoretical calculations. This will be applied to drug design and to refine X-ray and neutron diffraction structures of HCA2. 

Home Institution: Faculdade de Ciências e Tecnologia, UNL

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

Scientific Supervisor: Maria dos Anjos Macedo, FCT-Universidade Nova de Lisboa

Co-Supervisor: Claudio Luchinat, CERM, University of Florence and Carlos F. Geraldes, Universidade de Coimbra