The alternative processing of genomic loci through alternative splicing (AS) to produce multiple transcripts is a prevalent mode of gene expression regulation in multicellular organisms. It is related to essential biological processes and it has been long recognized that disruption of splicing mechanisms can cause disease, including cancer. Cancer arises from genetic and epigenetic alterations that interfere with essential mechanisms of the normal life cycle of cells, such as replication control, DNA repair and cell death. Multiple cancer-related alterations have been described to induce AS changes in tumor transcriptomes, which in turn impact their function and contribute to the pathological properties of tumors. The prevalence of AS in cancer genomes suggests that these alterations may be related to significant functional impacts and may explain some of the observed oncogenic properties. With the aim to address this question, we performed an exhaustive analysis of the functional impacts produced by AS changes in tumors. We described how cancer specific AS changes lead to shorter protein products. As a consequence, transcript isoforms expressed in tumors encode for fewer functional domains, i.e. there is a potential loss of the functional capacities of genes. Protein domains more frequently affected by AS belong to functional families classically affected by somatic mutations in tumors. Additionally, these functional losses are strongly associated to protein-protein interactions and affect partners of classical cancer drivers. Moreover, we observed that protein affecting mutations and splicing changes tend to occur in different patients, suggesting an equivalence between the mutations and splicing changes. Splicing alterations may thus recapitulate similar functional impacts to those observed through genetic alterations, namely protein affecting mutations and copy number alterations, more commonly associated with cancer. Transcriptome data thus shows that alternative splicing has a functional impact similar to other alterations, and may also play a driving role in cancer progression.

An ultimate challenge in biology is to understand the relationship between structure, function and dynamics of biomolecules in their natural environment: the living cell. Take as example the membrane that surrounds all living cells. Once believed to be a simple lipid bilayer that separates the interior from the exterior of the cell, it is now clear that the cell membrane is a highly complex, versatile, and essential signaling interface. Importantly, its function is crucially governed by the compartmentalization – in space and time – of a multitude of different molecules. However, our understanding on how the cell membrane dynamically organizes all these molecules to perform its function has been challenged by the lack of non-invasive techniques that provide access to the small spatial dimensions involved (the nanometer scale) in a dynamic fashion.

Optical nano-antennas are metallic nanostructures that concentrate light into bright nanoscopic hotspots. They can be viewed as nano-sources of illumination and therefore could be potentially used to visualize dynamic processes in living cells with nanometer resolution. In 2017, we designed a novel type of in-plane antennas and exploited them to monitor the diffusion of individual lipids on biological membranes. By using antennas of different gap sizes (down to 10nm in size), we revealed the existence of nanoscopic domains of lipids and cholesterol. These domains are as small as 10nm in size, and highly transient, with characteristics lifetimes around 100 microseconds. The existence of such nanodomains in living cells, also known as lipid rafts, have been predicted theoretically but never observed experimentally. Lipid rafts play a crucial role in many cellular processes that include signal transduction, protein and lipid sorting, and immune response among others. Understanding their formation, biophysical properties and relating their structure to their functional role are of paramount interest. Our nano-antenna breakthrough design provides an encouraging outlook to investigate the dynamics and interactions of lipids and raft-associated proteins.