Gabriel Herrera Oropeza


Academic and Work Experience Prior to Sept 2021 Programme Start

I completed my undergraduate degree in Biotechnology Engineering at Tecnológico de Monterrey in Mexico, and after graduating I worked as a Voluntary Research Intern in the Varela Lab at the Institute of Neurobiology of the National Autonomous University of Mexico (UNAM). I was awarded a scholarship from the Mexican Council of Science and Technology to pursue a master's degree in Neuroscience in Developmental Neurobiology at King's College London (2020-21).

PhD Programme- Year 1- MRes and Project Rotations

During my first year in the programme, I completed three rotation projects that covered different areas of stem cell biology:

  1. For my first rotation, I worked under supervision of Dr Francesca Spagnoli characterising the lineage dynamics of the pancreas mesenchyme. Employing single cell RNA sequencing (scRNA-seq) and in situ sequencing datasets of the embryonic mouse pancreas, I inferred the lineage trajectory of the pancreatic mesenchyme and found that there are multiple mesenchymal subpopulations arising from a common mesothelial origin.

  2. During my second rotation, I worked with Prof Oscar Marin investigating the role of PGC1a-associated mechanisms on gene expression in cortical interneurons. Using publicly available scRNA-seq and scATAC-seq datasets of cortical interneurons from the developing mouse cortex, I performed differential expression and transcription factor motif enrichment analyses to identify potential binding partners of PGC1a.

  3. For my final rotation, I joined the lab of Prof Benedikt Berninger to study changes in nuclear structure and chromatin compaction during glia-to-neuron conversion. I developed a high content image analysis framework that measuring morphological and structural features of the nuclei and combined with immunocytochemistry can infer cellular trajectories. Using this method, I identified changes occurring at the nuclear structure level following neuronal induction.

PhD Programme- Years 2 to 4 - Doctoral Studies

During my PhD, I will be co-supervised by Prof Benedikt Berninger and Prof Oscar Marin in a new collaborative project, which will focus on determining the molecular basis and milestones of human cortical interneuron migration.

Correct functioning of the cerebral cortex requires the coordinated activity of excitatory and inhibitory neurons (also called interneurons). Cortical interneurons are generated in the ventral forebrain during embryonic development and, consequently, need to follow a complex trajectory to reach the cerebral cortex. The migration of interneurons is a very accurate process, and small perturbations can result in miswiring of cortical circuits and contribute to disease, including neuropsychiatric disorders and epilepsy.

Our current knowledge of interneuron migration comes mainly from rodents and, only recently, brain organoids. Although mouse models recapitulate a variety of common features of neurogenesis, including the basic steps for the generation and migration of interneurons, there are significant differences between the mouse and human cortex. Brain organoids have emerged as a promising alternative to study human interneuron migration; however, they are still far from modelling migratory routes accurately. Hence, there is a clear need for an in vivo system that allows us to study the migration of human interneurons.

Therefore, this research aims at uncovering the migration behaviour of human cortical interneurons by using a xenotransplantation model in which human interneuron progenitors will be grafted into the subpallium of the developing mouse brain. Using this approach, we intend to uncover differences in the migratory features of human and rodent immature interneurons, and thereby shed light on the mechanisms that go awry in human brain diseases."

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