mRNA Formation and Function
I did my B.S. and M.S. in the Faculty of Pharmacy at University of Barcelona. I moved to the CBM-SO in Madrid to pursue my doctoral formation with Dr. Luis Enjuanes, one of the top world scientists in coronavirus research. My research topic was the antigenic structure and mechanisms of neutralization of TGE virus (TGEV), a member of the Coronaviridae family.
I did postdoctoral training in Mariano Garcia-Blanco’s laboratory at DUMC (US) where I remained as a senior scientific researcher for many years. This period was very exciting as we investigated the transcriptional activation of HIV-1, and at that time we knew very little about the “new” retrovirus. During this period, I learned in-deep knowledge about transcriptional regulation and RNA biology. Mariano Garcia-Blanco is an internationally recognized expert in the “RNA world”, specifically in the regulation of pre-mRNA splicing. My work at DUMC laid the foundations for my future scientific career. Our work on the HIV-1 field resulted in many valuable contributions to viral transcriptional regulation.
Between my postdoctoral training at Duke and before joining the CNB-CSIC, I participated in a two-year period in clinical research and HIV-1 related teaching at the Institute of Medical Microbiology (IMM) in Basel, Switzerland, to complete the investment recovery requirement, which is a condition of the National Research Service Award (Research Training in AIDS. NIAID, NIH). My research work during that stage focused on the development of genotypic and phenotypic methods for the detection of resistant variants of HIV-1. One of the objectives of the project was to develop a new diagnostic test for anti-viral resistance (now on the market through a biotech spin off company based in Switzerland).
In 2001, I joined the CNB-CSIC. From then on, I resumed the projects derived from my previous postdoctoral stage focused on the study of the mechanisms of regulation of gene expression. My initial interest in transcription was generalized to other stages of mRNA processing, especially to alternative splicing, to study the connections between both processes. In 2006, I moved to the IPBLN of Granada where I continued developing the study of the functional coupling between transcription and alternative splicing.
Finally, a few years ago and motivated by my continuing interest in applied research, I established an interesting collaboration with a research group of Pharmaceutical Technology of the Faculty of Pharmacy at the University of Barcelona aimed to the development of improved formulations of solid lipid nanoparticles with low toxicity capable of transporting DNA and RNA into the cell and generating a biological response. We are currently applying these SLNs to brain delivery.
The main scientific interest of the group focuses on the study of the molecular mechanisms that regulate the transcription and processing of precursor messenger RNA (pre-mRNA) and how these two processes communicate and interact for the correct control of gene expression.
Our current and future work considers that the coupling mechanisms allow the establishment of control points or quality controls that regulate the synthesis and processing of pre-mRNA. The proteins that act at the interface of these processes would serve as control point factors to regulate co-transcriptional splicing. In addition to studying the molecular events that regulate these interactions, we want to go further and provide new knowledge about the molecular mechanisms focused on the functional coupling of transcription and alternative splicing that act in pathological situations.
Our lab is currently focused on the following three main areas of research:
- Role of transcription/splicing factors in nervous system, neurodegenerative diseases, and cancer.
- The spatial organization and dynamics of transcription and pre-mRNA processing within the highly compartmentalized eukaryotic nucleus.
- Development of efficient and safe nanoparticles for DNA and siRNA delivery into cells.