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Niemann-Pick type C patient cell lysosome dynamics
Rare Lysosomal Diseases
Hereditary mutations that affect lipid metabolism can result in severe disorders, such as Niemann-Pick, Gaucher, Fabry or Tay-Sachs diseases. These conditions lead to lipid accumulation in lysosomes, but how this causes cellular dysfunction remains unclear, limiting the development of effective treatments.
We investigate how the cellular biophysical landscape is altered in these conditions and seek strategies to restore it, using advanced fluorescence microscopy, high-throughput spectroscopy, and chemical biology tools.
HIV Lipid Membrane
HIV is an enveloped virus, a virus surrounded by a lipid membrane. This membrane is essential for the virus to infect cells and presents unique chemical and biophysical properties. We study how HIV acquires its membrane at unprecedented resolution using super-resolution microscopy, single-particle tracking and biophysical imaging.
Importantly for human health, this membrane is targeted by naturally occurring antibodies. To understand this process, we collaborate with the groups of Edurne Rujas and José L. Nieva, applying advanced fluorescence methodologies to characterise the interaction between the viral membrane and antibodies.
Lipid diffusion in an HIV-1 assembly site
Biophysical Imaging
The biophysical properties of organelle membranes are key for cell function. However, the link between cellular health and membrane biophysics remains largely unknown. A major reason for this is the lack of accessible methodologies to investigate membrane biophysics in cellular contexts.
We work at the interface between method development and application to increase the accessibility of advanced microscopy. With this goal, we combine spectroscopy and microscopy approaches, characterise membrane fluorescence probes and develop software tools.
Fluorophore Behaviour
Fluorescence microscopy relies on fluorophores, dyes or proteins that emit light upon excitation. They can be used to visualise proteins, lipids, DNA and other biomolecules, but also to probe the cellular environment, reporting on membrane fluidity, potential or pH.
Even if fluorescence was first described long ago, the photophysical principles underlying it are not fully understood. As a result, fluorophores still face significant limitations, such as photoconversion (bleaching, blueing), which hinder the interpretation of quantitative microscopy data. To maximise their applicability in life science research, we characterise the behaviour of widely used fluorophores and develop strategies to circumvent these limitations.
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