Columbia Undergraduate Science Journal

Letter From The Editor-In-Chief

Kynnedy Smith — 2024-01-09

Kynnedy Simone Smith is the Editor-In-Chief for the 2022-2023 edition of the Columbia Undergraduate Science Journal.

Molecular Mechanisms and Clinical Features of Huntington Disease: A Fatal Neurodegenerative Disorder with Autosomal Dominant Inheritance

Neelabh Datta — 2024-01-09

Huntington disease (HD) is a fatal genetic disorder that affects the movement and cognition of affected individuals. It is inherited in an autosomal dominant manner, meaning that each child of a parent with HD has a 50% chance of inheriting the mutated gene. The mutation involves an expansion of a trinucleotide repeat (CAG) in the HD gene, which is located on the short arm of chromosome 4p16.3. The HD gene encodes a protein called huntingtin, which has an unknown function. The number of CAG repeats determines the severity and onset of the disease. Normal individuals have 26 or fewer repeats, while HD patients have 40 or more repeats. Individuals with 27 to 35 repeats do not develop HD, but they can pass on the mutation to their offspring, especially if the mutation is inherited from the father. Individuals with 36 to 39 repeats may or may not develop HD, depending on other factors. The more CAG repeats, the earlier the symptoms appear. HD is the most extensively studied neurodegenerative disorder with a genetic cause. There are genetic tests available to diagnose HD and to predict the risk of developing HD in asymptomatic individuals. There are also prenatal and preimplantation tests to prevent the transmission of HD to the next generation. HD is characterized by involuntary movements called chorea, which affect all muscles and impair all psychomotor functions. HD patients also suffer from cognitive decline and psychiatric symptoms, such as mood disorders and social changes. These symptoms are chronic and progressive, leading to complete dependence and death. Chorea can also be caused by other conditions, such as metabolic disorders or drug-induced side effects. Neuroimaging techniques, such as MR imaging, fluorodeoxyglucose positron emission tomography (FDG-PET), MR spectroscopy, and diffusion tensor imaging, can help to diagnose HD and monitor its progression. The pathophysiology of HD involves the loss of neurons and the dysfunction of neurotransmitter systems, especially the dopaminergic system. There is no cure for HD, but there are treatments to manage the symptoms and to improve the quality of life of HD patients. These include pharmacological interventions, such as dopamine receptor antagonists or depleters, and non-pharmacological interventions, such as psychological and social support. HD is a devastating disease that poses many challenges for patients, families, and healthcare providers. There is hope that gene-targeted therapies will be developed in the near future to stop or slow down the disease process.

Expression of Single mRNA Constructs Encoding Both CRISPR-Cas9 Protein and Guide RNAs for Future Gene Therapy Applications

Elvis Lang — 2024-01-09

The basis of many life-threatening diseases is disruption in key genes. In many cases, repairing these disruptions can prevent or reverse disease. The development of CRISPR-Cas9 technology, which consists of Cas9 nuclease directed to specific genomic locations by guide RNA (gRNA), has significantly progressed in the past decade and has shown signs of promise for treating diseases such as Alzheimer’s and cystic fibrosis. One integral issue of gene editing therapy is the method and effectiveness of delivery. Current approaches such as lentiviral and adeno-associated virus vectors suffer from either stable, constant expression of CRISPR components that causes unintended gene editing or an inability to efficiently carry large cargoes such as two independent genes: Cas9 and guide RNA. To begin to bypass these cargo limitations, we created a CRISPR-Cas9 mRNA structure that encompasses all of the necessary components for gene editing on a single RNA. These constructs consist of a promoter, followed by a Cas9 open reading frame, a triplex region from MALAT1 that protects the Cas9 open reading frame, and then either 1, 2, or 4 gRNAs that target specific reporters, with each gRNA between two self-cleaving ribozyme sequences. These constructs successfully drove Cas9 editing of two distinct reporters in human cells and thus open the door for many more experiments such as incorporation into various delivery constructs to further develop this technology for gene editing therapy.

Inside the Nucleon: Tomographic Interpretations and Universality of GPDs with DDVCS

Melinda Yuan — 2024-01-09

The goal of Double Deeply Virtual Compton Scattering (DDVCS) experiments is to better understand the internal structure of the nucleon. Previous attempts to resolve the internal structure of nucleons have resulted in electromagnetic form factors and parton distribution functions for elastic scattering and deep inelastic scattering processes, respectively. Generalized Parton Distributions (GPDs) are the latest attempt to unify these models of nucleon structure. The GPDs of DDVCS give us ability to investigate off of the diagonal where x ̸= ±ξ. The main goal of our analysis is to determine the best experimental setup in order to deduce the kinematic variables on which GPDs depend from the lab observables. The effectiveness of our data collection in the laboratory is by determined the physical kinematics, Q², Q^′2,t, x_i,ϕ_LM, ϕ_CMV, and θ_CMV. We can then run DDVCS experiments and collect data on observables to improve upon the current models for GPDs of the nucleon.