In this podcast Ron Levy discusses epistasis and drug resistance in HIV-1 with Jeff Townsend at Yale. The podcast was recorded in March 2020 and released in September 2020. Jeff is a computational and evolutionary biologist who is host of the new podcast series “EpistasisNet” available on Apple Podcasts.  The development of drug resistance in HIV is the result of primary mutations whose effects on viral fitness depend on the entire genetic background, a phenomenon called “epistasis”.  Ron talks about the recent work in his group using a co-evolutionary (Potts) model to provide direct confirmation of epistasis in HIV. Building on work described in a series of papers with HIVE collaborators, Ron’s group has shown that primary mutations leading to drug resistance can become highly favored (or entrenched) by the complex mutation patterns arising in response to drug therapy despite being disfavored in the wild-type background, and they provide the first confirmation of entrenchment for all three drug-target proteins: protease, reverse transcriptase, and integrase.1,2,3

  1. Biswas, Avik, Allan Haldane, Eddy Arnold, and Ronald M Levy(2019). Epistasis and entrenchment of drug resistance in {HIV}-1 subtype B. {eLife}, 8. DOI: 10.7554/eLife.50524. PMCID: PMC6783267.
    doi  |  pdf
  2. Flynn, William F., Allan Haldane, Bruce E. Torbett, and Ronald M. Levy(2017). Inference of epistatic effects leading to entrenchment and drug resistance in HIV-1 protease. Molecular Biology and Evolution, 34(6), 1291. DOI: 10.1093/molbev/msx095. PMCID: PMC5435099.
    doi  |  pdf
  3. Flynn, William F., Max W. Chang, Zhiqiang Tan, Glenn Oliveira, Jinyun Yuan, Jason F. Okulicz, Bruce E. Torbett, and Ronald M. Levy(2015). Deep Sequencing of Protease Inhibitor Resistant HIV Patient Isolates Reveals Patterns of Correlated Mutations in Gag and Protease. PLoS Comput Biol, 11(4), e1004249. DOI: 10.1371/journal.pcbi.1004249. PMCID: PMC4404092.
    doi  |  pdf

2020

Winter Transcriptomics
Genomics Workshop

This tutorial includes two segments:

  1. Introduction to and applications of transcriptomics and single cell RNA-seq
  2. 3D genome organization

2019 LIVE CELL IMAGING WORKSHOP

This tutorial includes three segments:

  1. 0:00  Introduction  — Greg Melikian
  2. 35:44 Fluorescence 101, Advanced live cell microscopy techniques — Yen-Cheng Chen
  3. 121:40  Single Particle tracking and Fluorescence-EM Image Correlation (CLEM) — Ashwan Francis

2019 CRYO-EM WORKSHOP

2019 HDX TUTORIAL

2019 NMR TUTORIAL

2018 RNA WORKSHOP

Karin and William presented this workshop on RNA at the 2018 Summer HIVE All-Hands Meeting.