JARA-OSEGUERA LAB
Our lab is interested in understanding the function and regulation of the molecular machines responsible for electrical signaling in the cells of our bodies – ‘ion-channel’ proteins that form pores across biological membranes to allow specific types of ions to rapidly move across them under exquisitely regulated circumstances, while excluding other types of ions from crossing. These rapid (> ten million ions per second for a single channel molecule) and selective flows of ions across membranes through ion channels are directly responsible, among many other essential functions, for the rapid conduction of signals across nerves and neurons, the timing for skeletal- and heart-muscle contraction, synaptic transmission, and setting the ionic composition inside cellular organelles required for metabolic, physiological, and developmental processes. It is therefore not surprising that ion channel disfunction is associated with many human pathologies.
To achieve all these functions, ion channel proteins must directly interact with distinct types of signals and then respond by opening or closing their ion-permeable pores. Some channels have evolved to open their pore upon binding to specific ligands made inside cells, such as intracellular second messengers or extracellular neurotransmitters. Other channels open their pores in response to signals coming from the environment and constitute the molecular basis for how we detect sound, touch, some tastes, temperature and harmful substances.
We have a limited understanding of the molecular mechanisms that channels use to control the state of their pore in response to the signals that they evolved to detect, or how they detect many of these signals in the first place. For many ion channels of outmost biological importance, we ignore which signals they actually detect, the relevant complexes they form with other biomolecules to effect signaling, and the time- and location-dependence of these relevant interactions in the context of a living cell or organism. As surprising as it may sound, many important ion channel genes remain unidentified.
We are interested in (1) understanding how the complex three-dimensional structure of molecular machines and their dynamic behavior depend both on the sequence of amino acids that they are composed of as well as on their surrounding (bio)chemical environment – and (2) in the consequences of these mechanisms for the life of cells and organisms. A large part of our work focuses on the family of Transient Receptor Potential (TRP) cation-permeable channels because they offer a window into remarkably diverse biological processes and biochemical mechanisms: with 27 different TRP channel genes in mammals – and somewhat different numbers in other vertebrate animals, invertebrates, algae and even yeast – these transmembrane proteins play essential roles in virtually every system in the human body, including lysosomal and ciliary function inside cells, bone formation, immune and skin cell function, heart muscle structure and function, blood pressure regulation, hormone secretion and the detection of sensory stimuli. Our current work focuses mostly on TRP channels that function as the biological thermometers in our body, and are also involved in pain and inflammatory signaling, establishing a link between the nervous and immune systems.