Super-resolution quantitative imaging of HIV fusion and its neutralisation by antibodies

Descripción del proyecto

Ver para creer: obtención de imágenes de la unión del VIH con anticuerpos

A pesar de su uso generalizado en biología celular, la microscopía óptica convencional tiene una resolución limitada de aproximadamente 250 nm. Por lo tanto, su idoneidad para estudiar virus como el VIH, que tiene un tamaño de 120 nm, es limitada. El proyecto financiado con fondos europeos FILM-HIV propone emplear técnicas de microscopía de fluorescencia de superresolución para estudiar la entrada de células víricas y el modo de acción de potentes anticuerpos anti-VIH que bloquean este proceso. Dado que el VIH es una de las enfermedades con mayor mortandad de nuestro tiempo, ya que causa aproximadamente un millón de muertes al año en todo el mundo, dilucidar su ciclo de infección es fundamental para identificar nuevas dianas terapéuticas.

Objetivo

Seeing is believing. Under that premise, optical microscopy has become one of the most prominent observation technologies in life sciences. However, the spatial resolution of conventional optical microscopes is limited to around 250 nm. This raises the question on how we can apply this technique to the study the human immunodeficiency virus (HIV), a 120 nm large particle that is responsible for 1 million deaths every year. It seemed impossible, since the spatial resolution limit is caused by the diffraction of light and therefore a fundamental physical barrier. However, the development of super-resolution (sub-diffraction) fluorescence microscopy techniques, an emerging field awarded with the 2014 Nobel Prize in Chemistry, is providing new tools that are awakening optical microscopy-based virus research.

My proposed project FILM-HIV (Fluorescence Imaging & Live Microscopy of HIV) aims to apply state-of-the-art advanced super-resolution microscopy techniques to monitor and study (i) viral cell entry, and (ii) the action mechanism of potent anti-HIV antibodies that are able to block this process. I, Pablo Carravilla, have chosen the Leibniz Institute of Photonic Technology in Jena, Germany, as my host institution to develop my project under the supervision of the renowned scientist Prof. Christian Eggeling, where I will be trained in highly advanced super-resolution microscopy and plasma membrane organization studies. As part of my research I will carry out a secondment at one of the best university biomedical institutions in Europe - the Medical Sciences Division of the University of Oxford. The acquired skills in combination with my knowledge on HIV, viral membranes and antibodies, will allow for a cutting-edge study of a process that is critical to the infection cycle of HIV, the causative agent of the most lethal pandemic of our times: the acquired immunodeficiency syndrome.