Sara Gonzalez Ortega
Academic and Work Experience Prior to Sept 2022 Programme Start
I obtained my BSc in Biochemistry with Professional Experience at The University of Manchester. During my studies, I completed a placement year at the University of California San Francisco at Guo Huang's laboratory to study the regenerative potential of the heart. During this time, I became fascinated by the striking regenerative potential displayed across the animal kingdom and how some of these mechanisms of regeneration are reiterated across ontogeny and phylogeny. For my final year project in Manchester, I joined Karl Kadler's laboratory to explore the circadian regulation of collagen fibrils in response to immune cells in the heart and lungs. Upon completing my undergraduate studies, I wished to pursue a career in academia dedicated to regeneration in a translational field.
PhD Programme- Year 1- MRes and Project Rotations
Rotation 1 - Senescence and Cardiomyocyte Survival
Supervised by Prof. Georgina Ellison, I created an inflamm-aging environment in vitro. I studied the effects of senolytic drugs on cardiomyocyte survival and proliferation by co-culturing human iPSC-CMs with senescent cardiac stromal progenitor cells.
Rotation 2 - mRNA Delivery and CRISPR/Cas9 based strategies to improve homologous recombination
Supervised by Prof. Mauro Giacca, I used a CRISPR/Cas9 homologous recombination (HR) reporter system to measure HR events in the heart. My work also involved performing in vitro transcription (IVT) reactions to synthesize full-length mRNA transcripts of a protein enhancing HR, and delivering them via lipid nanoparticles to primary cardiomyocytes as an alternative to adeno associated viral vectors (AAVs).
Rotation 3 - Unraveling the NOX4 Transcriptome
With Dr. Alessandra Vigilante, I delved into R language basics. My focus was on dissecting the global transcriptional program associated with the enzyme NOX4. I performed a data integration pipeline to analyze bulk RNA-seq, ATAC-seq, and Chip-seq datasets, revealing epigenetic signatures and regulatory networks.
Through these diverse rotations, I have cultivated a robust skill set encompassing laboratory techniques, genetic manipulation, and bioinformatics analysis.
PhD Programme- Years 2 to 4 - Doctoral Studies
For my Ph.D., I am excited to contribute my expertise and passion to future endeavors in cardiovascular research. In Mauro Giacca's laboratory I will research the efficacy of pro-proliferative microRNAs in primary mouse cardiomyocytes and human myocardial slices. Heart failure (HF) results from cardiac damage and subsequent loss of contractile function following injury. Some organisms, like zebrafish or neonatal mice, can regenerate the heart via proliferation of pre-existing cardiomyocytes.
On the opposite, the mammalian adult heart is largely a post-mitotic organ, cardiomyocyte replication stops at birth and their endogenous regenerative capacity is not sufficient to compensate the loss of myocardium. Despite extensive research on regenerative medicine, cell or gene therapies adopted in clinical settings have not yet achieved significant improvements in patient’s heart function. One key challenge lies in finding a master regulator that stimulates cardiomyocyte proliferation. MicroRNAs (miRNAs) are recognized pleiotropic regulators of gene expression. Prof. Mauro Giacca's laboratory identified various human-specific miRNAs that can enhance cardiomyocyte proliferation.
My PhD aims to understand the biology of pro-proliferative miRNAs, from their molecular mechanisms to potential clinical interventions.
