Jose Luis Cabrera Alarcón, PhD
I joined GENOXPHOS group to develop and strength the bioinformatic lines of investigation. Mitochondrial respiratory complexes are precise protein machines, in which any mismatch can have bioenergetic consequences. Bearing this in mind, the diploid condition of nuclear OXPHOS genes represents an unexplored potential source of functional variability within the OXPHOS components. I am exploring this possibility supported by a Human Frontier Science Program (HSFP) project. I am investigating the existency of potential mechanisms for the regulation of the expression of alternative alleles. This implies the development of ad hoc methodology for the analysis of single cell RNAseq data. In addition, I am developing a pipeline of in silico models of the respiratory chain complexes to estimate the structural and functional effect of specific aminoacidic changes.
Carolina García-Poyatos, PhD
I am working under a cooperative project between GENOXPHOS group and the group headed by Dr. Mercader at CNIC in the investigation of the physiological relevance of alternative isoforms of the subunit 7a (Cox7a1, Cox7a2 and Cox7a2L or SCAF1) of the cytochrome c oxidase or complex IV (CIV). CIV catalyzes the last step of the mitochondrial electron transport chain transferring electrons from cytochrome c to oxygen and forming water. CIV may be found in monomeric form, dimers, multimers and super assemble to other complexes forming part of the Q-respirasome and the N-respirasome (Cogliati and Calvo, et al. Nature 2016). Using zebrafish and mouse models, I study the role of supramolecular structures of CIV at molecular and physiological level. The best-known mechanism of supra organization of CIV is its super assembly with CIII, mediated by Scaf1. Absence of Scaf1 in zebrafish resulted in the absence of super complexes CIII-CIV and an impairment in the utilization of metabolic resources (García-Poyatos et al. EMBO Rep. 2020).
Cogliati and Calvo, et al. Nature 2016
Garcia-Poyatos et al. EMBO Rep. 2020
Pablo Hernansanz Agustín, PhD
My research is focused on the role of Na+ in the regulation the oxidative phosphorylation system, in particular, related to the formation of supercomplexes, ubiquinone and cytochrome c dynamics and pool behaviour, electron flux and the production of reactive oxygen species (ROS). We recently published that Na+ can act as a second messenger by regulating the inner mitochondrial membrane (IMM) fluidity, lowering the electron transfer from complex II to complex III, but not inside supercomplexes, and increasing the production of ROS by complex III. This mechanism controls acute hypoxic adaptations such as hypoxic pulmonary vasoconstriction. Actually, I am exploring the implication of this pathway in the onset and/or development of a variety physiological and pathophysiological scenarios.
María Concepción Jiménez Gómez, PhD
I joined GENOXPHOS group after a first step in my career working in the pharma industry. I am aimed to explore and develop the translational potential of the basic research discoveries of the group by identifying potential pharmacological targets and develop genetic tools of potential use in the treatment of human diseases. In addition, my work is focused on the development and assessment of translational potential and patentability of techniques and know-how of the group developed in the group to make them available to industry partners. GENOXPHOS is currently developing projects with leaders in the pharmaceutical industry, including Astrazeneca and Minovia Therapeutics.
Andréa Curtabbi, MD
I joined GENOXPHOS lab after obtaining my MD degree from the University of Turin. My research is focused in understanding how the assembly and the turnover of respiratory Complex I can affect mitochondrial function and ROS production. In collaboration with the proteomic unit at CNIC, I am looking for candidate genes that are important for Complex I stability and activity that may have a role in human disease. By using mouse models of Leigh syndrome, an inheritable mitochondrial disorder, I am also investigating how genetic defects in oxidative phosphorylation led to neuromuscular and cardiovascular pathologies.
Yolanda Martí Mateos
I joined the group as predoctoral student working on several genetic models where structural or functional changes in mitochondria lead to beneficial effects for the organism in the context of diverse pathologies. I am focused in understanding the cardioprotective effects exerted by the inhibition OMA1, a mitochondrial stress-protease, and extending, its protective potential in nobel clinical contexts. Additionally, I study the role of Fgr, an src-type tyrosine kinase in regulating mitochondrial function, inflammation and fat metabolism. My final aim is to develop tools of clinical relevance in preventing heart failure and obesity.
Raquel Justo Méndez
I am focused on the variability of mitochondrial DNA (mtDNA) and its effect in the OXPHOS system behavior and mitochondrial ROS (mtROS) generation. OXPHOS system is the only process in animal cells with components encoded by two genomes, mtDNA and nuclear DNA (nDNA). It means that mtDNA-encoded proteins have to physically assemble with the nuclear-encoded ones to build the respiratory complexes. This constraint imposes a close-fitting co-evolution of both genomes. MtDNA random mutation in somatic cells followed by somatic segregation and amplification is a common phenomenon during ageing or under pathological conditions as cancer. I use complastic (animals with identical nuclear background but alternative wild type mtDNAs) and heteroplasmic mice (animals with more than one variant of non-pathological mtDNA co-existing in the same cytoplasm) to investigate the impact of key nuclear genes on the segregation of mtDNAs and then the OXPHOS performance and the mtROS handling.
Raquel Martínez de Mena, PhD
I completed my Doctoral Thesis in Science at the Universidad Autónoma de Madrid and performed several years of laboratory work at the IIB in Madrid. Then I joined the GENOXPHOS group at CNIC as a technician specialized in cell culture and biochemical and molecular biology techniques.
Modified from Sci Adv. 2020 Jul 29;6(31)
María del Mar Muñoz Hernández
I joined GENOXPHOS after finishing my training as laboratory technician. In the group I am responsible for several aspects of the research with special expertise in handling experimental animal models including husbandry breeding and genetic characterization and with special training in surgery, metabolic and behavioral analysis.
Eva Raquel Martínez
I joined GENOXPHOS after several years of work in different research laboratories. I am working as a technician with special expertise in histological analysis to visualize cellular damage in different tissues. I am trained also in molecular biology methods and in handling experimental animal models.