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@@ -160,12 +160,6 @@ Compared to naïve cells, memory cells:
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naïve cells
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* evolve over time to respond even more strongly to their antigen
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-:::
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-
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-## Memory cells are a problem for immune suppression
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-
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-\large
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-
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Result:
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\normalsize
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@@ -175,22 +169,23 @@ Result:
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* Dosage cannot be increased indefinitely without compromising the
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immune system's ability to fight infection
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+:::
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+
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## We need a better understanding of immune memory
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-* Cell surface markers of naïve and memory $\mathsf{CD4}^{+}$ T-cells
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- are fairly well-characterized
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-* But internal mechanisms that allow memory cells to respond
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- differently to the same stimulus (antigen presentation) are not
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- well-understood
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+* Cell surface markers fairly well-characterized
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+
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+* But internal mechanisms poorly understood
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. . .
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-* A reasonable hypothesis is that some of these mechanisms are
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- epigenetic: using histone marks or DNA methylation to regulate the
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- expression of certain genes
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-* We can test this hypothesis by measuring gene expression (using
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- RNA-seq) and histone methylation (using ChIP-seq) in naïve and
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- memory T-cells before and after activation
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+\vfill
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+
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+\large
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+
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+**Hypothesis:** Epigenetic regulation of gene expression through
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+histone modification is involved in $\mathsf{CD4}^{+}$ T-cell
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+activation and memory.
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## Experimental design
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@@ -205,6 +200,27 @@ Result:
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Data generated by Sarah Lamere, published in GEO as
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[GSE73214](https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE73214)
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+## Time points capture phases of immune response
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+
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+\centering
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+
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+<!-- { height=75% } -->
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+
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+## Why study these histone marks?
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+
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+::: incremental
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+
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+* **H3K4me3:** "activating" mark associated with active transcription
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+
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+* **H3K4me2:** Correlated with H3K4me3, hypothesized as a "poised" state
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+
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+* **H3K27me3:** "repressive" mark associated with inactive
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+
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+* All 3 involved in T-cell differentiation, but activation dynamics
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+ unexplored
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+
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+:::
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+
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## ChIP-seq sequences DNA bound to marked histones[^chipseq]
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\centering
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@@ -213,10 +229,6 @@ Data generated by Sarah Lamere, published in GEO as
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[^chipseq]: [Furey. "ChIP-seq and beyond: New and improved methodologies to detect and characterize protein-DNA interactions". In: Nature Reviews Genetics (2012)](http://www.nature.com/articles/nrg3306)
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-## H3K4me2, H3K4me3, H3K27me3
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-
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-Why? <!-- TODO -->
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-
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## A few intermediate analysis steps are required
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