HoatlinCONJ606:Materials 2018

Class Focus, Fall 2018

2. Genomic instability

Organizational Meeting: Introduction and Scheduling

Evaluation Forms

• Evaluation Form MC and Discussion Leader
• Evaluation Form Presenter 1(Intro)
• Evaluation Form Presenter 2

• Evaluation Form MC extra

Week 2:

October 1-5, 2018

Papers

The Neuronal Gene Arc Encodes a Repurposed Retrotransposon Gag Protein that Mediates Intercellular RNA Transfer
Link to Paper

Bonus Materials

Brain Cells Share Information With Virus-Like Capsules
Link to Paper and

Week 3:

Papers

High speed of fork progression induces DNA replication stress and genomic instability
Link to Paper

Bonus Materials

Superfast DNA replication causes damage in cancer cells
Link to article

Week 4: A Liquid Phase of Synapsin and Lipid Vesicles

Papers

A Liquid Phase of Synapsin and Lipid Vesicles

Bonus Materials

Phase Changes in Neurotransmission

Supplementary Materials and Figures for the Paper

Week 5

Papers

Parkin and PINK1 mitigate STING-induced inflammation

Overview

PTEN-induced kinase 1 (PINK1) and the protein Parkin work in concert to initiate autophagy of dysfunctional mitochondria (also termed "mitophagy.") Mitochondria dysfunction is linked to autism spectrum disorder, heart disease, and Parkinson's, as well as other conditions. Here, Sliter et al show that unresolved mitochondrial damage leads to ill effects such as inflammation and neurodegeneration. Typically, PINK1/PArkin function is sufficient to combat mitochondrial dysfunction, but an absence of these proteins leads to a diseased state in which dysfunctional mitochondria are not repaired or eliminated. In this study, PINK1/Parkin knockout mice were exposed to mitochondrial stress through excess physical activity or by breeding with mice containing mutated mitochondria. PINK1/Parkin knockouts were unable to compensate for mitochondria stress and exhibited inflammatory responses mediated by the STING pathway (an important pathway in innate immunity which functions by recognizing exogenous DNA and activating a type I interferon response.) Following mitochondria stress, PINK1/Parkin mice showed elevated type I interferon response. These mice also showed loss of motor function and neurodegeneration. Crossing these mice with STING knockouts reversed this response (that is, PINK1/Parkin/STING knockouts did not exhibit an increase type I interferon response.) The detrimental effects upon motor and neuron function were also reversed. Thus, this study represents an important discovery related to the mechanism of PINK1/Parkin and the STING pathway in Parkinson's disease, suggesting that failure to maintain mitochondrial health through mitophagy is a main contributor to developing Parkinson's.

Week 7: Platelet-targeted dual pathway antithrombotic inhibits thrombosis with preserved hemostasis.

Papers

Platelet-targeted dual pathway antithrombotic inhibits thrombosis with preserved hemostasis

Bonus Materials

Supplementary Perspective for the Paper

Week 8:

Paper

Heterogeneity and interplay of the extracellular vesicle small RNA transcriptome and proteome

Bonus Materials

EVs, they're so hot right now! Here's a recent review of the field that emphasizes why these findings are so important:

Focus on Extracellular Vesicles: Introducing the Next Small Big Thing

Recent (2018) paper demonstrating the power of EVs as drug delivery platforms:

Efficient RNA drug delivery using red blood cell extracellular vesicles