Jesus, a sophomore studying Neuroscience at the University of California, Los Angeles (UCLA), studied the role of LRP1 and LDLR in astrocyte-neuron interaction.
This study builds upon prior research demonstrating that LRP1 and LDLR receptor knockdowns on neurons lead to synaptic loss and neurodegeneration, implicated in psychiatric disorders. At the Broad Institute, you will encounter yourself with remarkable research, all for the same purpose of improving medicine. Not only will you find highly reputable labs but also outstanding individuals who are willing to put effort into making you become the best version of yourself. The most valuable thing I learned is always to question every step along the way and to think as a scientist. We sought to validate synaptic loss using CRISPRi to deactivate LRP1 and LDLR receptor promoters. Utilizing Single RNAs for both receptors alongside a non-target control group, we employed Western blotting to assess synaptic marker protein levels, aiming to confirm potential synaptic marker protein expression loss. Quantitative-Qpcr was conducted upon samples to validate gene knockdown of LRP1 and LDLR. With pluripotent stem cells, differentiation into single neurons using a 2-D monolayer method was co-cultured with mouse-derived astrocytes, emulating an in vivo environment. Our study seeks to affirm previous findings regarding the inhibition of cholesterol and its impact on neuronal deficits. Employing computer programming, we analyzed data and performed statistical assessments. Future work would be to extend the neuron differentiation protocol from 14 to 30 days, enabling a more comprehensive evaluation of synaptic protein concentrations via the same methods. This extension would enhance our understanding of cholesterol inhibition's effects on neuronal structure and function. In conclusion, our research offers insight into the intricate relationship between lipid metabolism and synaptic integrity, potentially advancing therapeutic strategies for psychiatric disorders.
Project: Role of LRP1 and LDLR in astrocyte-neuron interaction
Mentor: Matthew Tegtermyer
PI: Nehme Lab, Stanley Center of Psychiatric Research