iBB

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).

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.