Curriculum
Module 17 · 75 min
Methods: Microscopy, Omics & Genome Editing
What you actually need to read a modern cell-biology paper.
CoreClinicalResearch
Topics
What this module covers
- 01Light microscopy: confocal, light-sheet, super-resolution (STED, SIM, SMLM)
- 02Cryo-EM and cryo-electron tomography
- 03Bulk vs single-cell RNA-seq; spatial transcriptomics
- 04Mass-spectrometry proteomics and phosphoproteomics
- 05CRISPR-Cas9, base editing, prime editing, Cas13
- 06Functional genomics screens (CRISPRi/a, Perturb-seq)
Deep dives
Lesson sub-pages
Learning objectives
By the end of this module you will be able to
- L01Choose the right imaging modality for a given resolution/depth question.
- L02Distinguish a CRISPR knockout, knockdown, base edit and prime edit and explain when each is appropriate.
- L03Critically read a single-cell RNA-seq figure (UMAP, marker genes, batch effects).
Expected takeaways
What you should walk away believing
- →Single-cell omics changed cell biology in the way GFP did in the 1990s.
- →Base/prime editing avoid double-strand breaks — likely the safer in-vivo platform for most monogenic indications.
- →Cryo-ET routinely visualises macromolecular complexes inside cells in their native context.
Core summary
At the Core level
You cannot evaluate cell-biology papers — or modern translational evidence — without a working knowledge of the methods. This module gives the operating principles, the strengths, and the failure modes for the techniques that produce most current results.
Evidence-graded claims
Claims, scored A–F
A
Base editing avoids double-strand breaks
Definitional; uses nickase + deaminase.
C
Single-cell atlases capture all cell types in a tissue
Sampling bias, dissociation bias, rare populations missed.
D
AlphaFold-Multimer reliably predicts all protein-protein interactions
Variable; better for stable complexes, worse for transient and antibody-antigen.
Quiz
Check your understanding
Q1. Which technique resolves macromolecules inside intact frozen cells at near-atomic resolution?
Q2. Prime editing differs from base editing because it:
Flashcards
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Front
STED principle?
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Suggested reading
Primary literature
- Search-and-replace genome editing without double-strand breaks (prime editing) — Anzalone et al., Nature 2019 ↗
- The promise of single-cell transcriptomics — Tanay & Regev, Nature 2017 ↗