The joining of coding exons in a gene is a fundamental process in all types of mammalian cells. This complex process is carried out by cellular macromolecules called spliceosomes and associated splicing factors. Different cells can produce unique splicing patterns, leading to the production of distinct protein isoforms and ultimately defining the cell's function and characteristics. Although it is known that the regulation of RNA splicing plays a crucial role in determining cellular identity, how it is still unknown what determines the regulatory outcome. Our research addresses the regulatory mechanisms of RNA splicing, focusing on the identification of cell-specific splicing factors and how they interact with the spliceosome to guide splicing choices.

What triggers the choice of a cell to include or exclude an exon? Several factors contribute to this decision, including the presence of specific regulatory proteins, the sequence of the RNA molecule itself, and the inter and intra-cellular environment at the time of splicing. But at the operational level it is highly possible that some logical components (for eg. evolutionarily conserved splicing factor) to carry out the decision of alternative splicing. Through this logic, cells can operate in a dynamic manner, modifying the splicing patterns of their RNA in response to changes in their environment or developmental stage. This allows for a high degree of flexibility in gene expression and protein diversity. We aim to gain a deeper understanding of this logic through cellular and computational models to dissect the complex interaction between splicing factors, RNA sequences, and cellular environments. Our goal is to decode the 'language' of alternative splicing and to establish a 'grammar' for predicting splicing outcomes under various conditions.

There is no single splicing factor regulating splicing of a single gene or an exon. Instead, multiple splicing factors work in a complex interplay to control the splicing process. These factors can interact with each other, potentially affecting multiple genes or exons simultaneously. Understanding structure of this network is not only important for understanding how cells achieve their complex and diverse functions, but also for shedding light on how dysregulation of this network could lead to diseases. With the right tools and methodologies, we can begin to unravel this complex network and its role in cellular function. Because cells make up tissue and organs, and organs are often interconnected, understanding these networks can further provide insight into how different organs communicate and coordinate with each other. This could further our understanding of how diseases affect multiple organs and potentially lead to more effective treatments. In this research theme, we use novel spliceomics approaches to study the structure and dynamics of splicing networks. We aim to identify key splicing components and interactions that influence cellular function across different organs.