Biointeractomics

Our research is focused on the structural and functional analysis of biological macromolecules, including protein-protein and protein-nucleic acid interactions, which are crucial for a broad range of cell processes, and post-translational modifications of proteins. We center particularly on mitochondrial cytochrome c (Cc)–a protein which plays a double role in redox metabolism and programmed cell death–and try to understand the evolution of cell death by identifying novel targets of Cc. In addition, we study the role of some intrinsically disordered proteins in liquid-liquid phase separation. Large part of our research is based on Nuclear Magnetic Resonance (NMR) analysis, which is particularly useful on our metabolic profile study of agri-food.

The work of the Biointeractomics group, at the Institute of Chemical Research of Seville, is multi- and interdisciplinary. In collaboration with worldwide laboratories, we apply a broad diversity of methodologies and techniques ranging from molecular and cell biology to biochemistry, biophysics, structural biology and computational chemistry.

Main research areas

1. Structural Insights into Biointeractomics of DNA Damage

When living cells are damaged, respiratory cytochrome c (Cc) escapes its natural mitochondrial environment to the cell cytosol and nuclei. In the cytosol, it activates apoptotic pathways, while in the cell nuclei it interacts with proteins involved in the DNA damage response, DNA replication and transcriptional regulation.

Our work focuses in understanding the molecular basis of the interaction of respiratory Cc with nuclear proteins such as ANP32B, SET/TAF-Iβ, nucleophosmin (NPM1) upon DNA damage, and how post-translational modifications on these proteins shape their functionality. This study employs cell biology, biophysical structural techniques, and molecular dynamics simulations to elucidate the atomic and cellular implications of these interactions, providing insights that may have significant implications for therapeutic strategies in cancer and other diseases.

2. The Interplay of RNA-Binding Proteins and Biomolecular Condensates in Neurodegenerative Diseases

In the context of neurodegenerative diseases, we study the interplay between TIA-1, an RNA-binding protein associated with stress granules, in the pathological aggregation of Tau, an intrinsically disordered protein linked to Alzheimer’s disease. TIA-1 enhances Tau’s liquid-liquid phase separation (LLPS), facilitating its transition from liquid condensates to toxic oligomers. This interaction suggests a mechanistic link between RNA-binding proteins and Tau aggregation, providing new insights into potential therapeutic targets for neurodegenerative disorders.

Some of the biophysical techniques that we use are: Nuclear Magnetic Resonance (NMR), Circular Dichroism, Biolayer Interferometry, Isothermal Titration Calorimetry or Fluorescence Microscopy.

3. NMR-based Metabolomics of Agri-Food Products

The aim of this line is to automate trademark product traceability and identification throughout the supply chain by the ascription of a digital fingerprint. It proposes an innovative approach based on the integration of cutting-edge omics technologies such as NMR with the use of statistical and machine learning algorithms, to obtain a characteristic metabolic pattern of each product (fingerprint) and create an Artificial Intelligence (AI) based model capable of classifying and verifying the different analyzed products.

In this new paradigm, NMR would act as the “sensory” technology, and the AI-based classifier, as a “brain” capable of extracting the differential information and characteristics that would allow the samples to be automatically classified: in other words, the identification of a fingerprint. Using this methodology, it is possible to obtain a metabolic pattern characteristic of the sample, identify potential biomarkers related to contamination, certify geographical indications of products, and study product traceability.