iBB

Ana Melo obtained a Visiting Researcher Award from the São Paulo Research Foundation (FAPESP), Brazil. This funding allowed her to stay in Brazil during October 2023 for: i) Visiting the Laboratory of Professor Rosangela Itri at Physics Institute, University of São Paulo (IFUSP); ii) Performing measurements at the Brazilian Synchrotron Sirius -4th Generation (Campinas, São Paulo State); Iii) Participating in the 47th Annual Meeting of Brazilian Biophysical Society (SBBf, Unicamp Convention Center from 19 to 22 October 2023).

Lipid hydroperoxides have recently been recognized as key mediators of diseases (such as neurodegenerative disorders or Type II diabetes) and cell death. In a recent work, structural and dynamic perturbations induced by the hydroperoxidized POPC lipid (POPC-OOH) in fluid POPC membranes were addressed using advanced small-angle X-ray scattering (SAXS) and fluorescence methodologies. Notably, this multidisciplinary approach revealed that the hydroperoxide group located at the membrane interface, promotes a higher membrane hydration and microviscosity, with a strikingly lower order and bending rigidity, an unusual trend in membrane biophysics, which ultimately compromises membrane structure organization. This international work co-led by Ana M. Melo (BSIRG-iBB) and Rosangela Itri (Institute of Physics, University of São Paulo) was recently published in Langmuir and involved other BSIRG-iBB researchers (Ana Coutinho, Alexander Fedorov and Manuel Prieto).

Intrinsically disordered proteins/regions (IDPs/IDRs) are widespread in the human proteome and play critical roles in distinct biological processes and dysfunction. Contrary to the classical “structure–function” paradigm, IDPs lack stable secondary/tertiary structures under physiological conditions, and instead adopt a dynamic ensemble of multiple conformations. Moreover, several neurodegenerative disorders are associated with the pathological self-assembly of neuronal IDPs, including tau (Alzheimer’s disease), α-synuclein (Parkinson’s disease), and huntingtin exon 1 (Huntington’s disease). Therefore, there is an emerging medical interest in understanding their physical and structural features. However, their characterization is inherently challenging by traditional ensemble and time-averaging methodologies. A recent review co-authored by Ana Melo from BSIRG-iBB, and published in Frontiers in Molecular Neurosciences the advantages of employing cutting-edge single-molecule fluorescence techniques are discussed to characterize the conformational ensemble of neurodegeneration-promoting IDPs under normal and disease conditions to obtain insights into their gain- or loss-of-function.

A position is open to hire a doctorate researcher within the framework of the FCT-funded SingleMolHTTex1 project. The overall aim of this project is to provide a detailed understanding of the initial binding steps of Huntingtin exon1 (HTTex1, with an expanded polyglutamine repeat) to biological membranes. A complementary set of single-molecule fluorescence techniques will be used to obtain insights into the physical/structural features of aggregation-prone states of HTTex1 at the membrane surface. Importantly, the results of this frontier project may assist in the rational design of inhibitors to treat and/or prevent Huntington’s disease. The work will be carried out under the scientific guidance of Dr. Ana M. Melo and at BSIRG (at CQFM and iBB), IST. More information on the position and how to apply can be found here under the acronym SingleMolHTTex1 and email to anammelo@tecnico.ulisboa.pt. The application deadline is February 12th, 2019.

Ana Melo delivered an oral presentation at the 1st ML4NGP Meeting on Machine Learning and Non-Globular Proteins, Bratislava- Slovakia (July 2023). Her presentation was focused on mapping the structural transitions of the flanking polyQ regions in huntingtin exon 1 upon membrane binding, and its implications in Huntington´s disease. 

AM Melo was also elected for co-Leader of Working Group 4 of this ML4NGP COST-action. This group aims to improve the functional characterization of non-globular proteins (NGPs) and to understand the major questions involving NGPs. They include “conformational heterogeneity, evolution, conserved motifs, protein-protein interactions, liquid–liquid phase separation (LLPS) and involvement in neurodegenerative diseases.”

Ana M Melo participated as secondary proposer in the grant application of the COST Action: Non-globular proteins in the era of Machine Learning (ML4NGP). The action was recently funded and started in October 2022. Ana M Melo was selected to be part of the Management Committee and the first meeting already took place with decisions on the budget allocation/organization and future meetings. This COST-action is focused on non-globular proteins that comprise “intrinsically disordered regions, repeats, low-complexity sequences, aggregation-prone and phase-separating sequences, and are implicated in a range of age-related diseases”. The network combines both experimentalists and computational researchers. 

Ana M. Melo was a recipient of a 2022 Biophysical Travel Award for Scientists within 10-years after completing the PhD. She was honored during the Travel Awardee Reception by the Society’s Committees for Inclusion/Diversity and Professional Opportunities for Women. This highly competitive award covered her travel expenses to San Francisco, California (US).

Ana Melo gave an invited talk during the XVII Meeting of the Portuguese Society for Neuroscience, at Coimbra, 1 - 3 December, 2021. She presented recent work focused on characterizing the distinct conformational dynamics of the flanking polyQ regions in the membrane-bound state of Huntington exon 1, and its role in Huntington´s disease. Her presentation was in the framework of the SPB Symposium: “A biophysical perspective on degenerative diseases: protein assembly and phase separation”, together with Sandra Macedo Ribeiro (IBMC- i3S) and Salvador Ventura (IBB-Universitat Autonoma de Barcelona).