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N-terminal domain of rRNA methyltransferase enzyme RsmC is important for its binding to RNA and RNA chaperone activity
Ribosomal RNA modification enzyme, Ribosomal small subunit methyltransferase C (RsmC) plays a dual role of methylating the exocyclic amine of G1207 of 16S ribosomal RNA and functioning as an RNA chaperone. RsmC carries Methyltransferase active C-terminal domain and catalytically inert N-terminal domain. This project is focused on identifying the importance of the N-terminal domain and its role in the RNA chaperone activity. Site-directed mutagenesis was used to delete the C-terminal domain. Mutant proteins were purified
using affinity chromatography. Mutant protein was found to have a lower affinity to both strands of helix 34 that carries G1207. Similarly, the RsmC deletion mutant influenced the annealing of helix 34 strands. These observations reveal the molecular mechanism of RNA chaperone activity of RsmC and its role in ribosome biogenesis.Analysis of whole body inducible HUWE₁ knockout in mice
HUWE₁ is a HECT-domain ubiquitin E3 ligase that plays numerous roles in cellular processes by promoting degradation of its substrates. Although it has been discovered that mutations in HUWE₁ can lead to countless cancers or human diseases, given a number of the substrates with various cellular functions, the in vivo role of HUWE₁ remains elusive. Importantly, conventional HUWE₁ gene knockout (KO) leads to embryonic lethality, which makes it difficult to analyze the role of HUWE₁ in different tissues and organs. Here, we created whole body inducible HUWE₁ knockout mice, in which HUWE₁ was acutely deleted in 4-week-old mice. We show that inducible HUWE₁ KO did not result in lethality, and we will discuss the phenotypes of the KO mice.
The effects of physical activity on sleep quality in Parkinson’s disease patients
Parkinson's disease (PD) is a widespread neurodegenerative disease characterized by motor and non-motor deficits. Physical activity (PA) has been shown to improve sleep in healthy populations. However, individuals with PD generally show low levels of activity. The purpose of this study was to analyze survey-based outcomes in the Fox Den survey database for associations between sleep and physical activity variables in PD and individuals without PD. Data analysis & hypothesis testing was done using R and python statistical analysis software. There was a significant difference between sleep disturbance levels amongst PD vs nPD. Additionally, the days and hours of PA per week were higher in nPD than PD. Individuals with PD showed greater incidence of sleep disturbance and less physical activity than persons without PD.
In vitro model of myelination, demyelination, and remyelination of oligodendrocytes
Multiple Sclerosis, a neurodegenerative disease is caused by the degradation of oligodendrocytes in the Central Nervous System (CNS) which results in the degradation of the neuronal myelin sheath. This study is about an in vitro model regarding myelination, demyelination, and remyelination of myelin-producing oligodendrocytes. PMA, a cell differentiating agent is administered to study various levels of myelination. Lysolecithin, a cell membrane integrating phospholipid, is used to study demyelination. The delivery of N-acetyl aspartate (NAA) using nanoparticles is used for the study of remyelination. The different levels of myelin production are verified through analysis of myelin-associated mRNA, proteins lipids via qRTPCR, Western Blots, and TLC and GC/MS. The increase in myelin suggests that the remyelination therapy model was successful.
Mitochondrial dynamics in APP/PS₁ mice models
The goal of my research is to identify therapies for Alzheimer's disease (AD). I have hypothesized that enhancing one carbon metabolism with the methyl donor betaine will improve mitochondria in a mouse model of AD by decreasing the levels or activity of DRP₋₁. This protein causes excess fission of mitochondria in AD which generates smaller mitochondria that are unable to make enough energy. I am testing my hypothesis by administering betaine (1%) in drinking water to 1-month and 3-month (n=3) AD mice and measuring the effects on DRP₋₁ and mitochondrial size.