More intro polishing

presentation.mkdn

@@ -160,12 +160,6 @@ Compared to naïve cells, memory cells:
   naïve cells
 * evolve over time to respond even more strongly to their antigen
 
-:::
-
-## Memory cells are a problem for immune suppression
-
-\large
-
 Result:
 
 \normalsize
@@ -175,22 +169,23 @@ Result:
 * Dosage cannot be increased indefinitely without compromising the
   immune system's ability to fight infection
 
+:::
+
 ## We need a better understanding of immune memory
 
-* Cell surface markers of naïve and memory $\mathsf{CD4}^{+}$ T-cells
-  are fairly well-characterized
-* But internal mechanisms that allow memory cells to respond
-  differently to the same stimulus (antigen presentation) are not
-  well-understood
+* Cell surface markers fairly well-characterized
+
+* But internal mechanisms poorly understood
   
 . . .
 
-* A reasonable hypothesis is that some of these mechanisms are
-  epigenetic: using histone marks or DNA methylation to regulate the
-  expression of certain genes
-* We can test this hypothesis by measuring gene expression (using
-  RNA-seq) and histone methylation (using ChIP-seq) in naïve and
-  memory T-cells before and after activation
+\vfill
+
+\large
+
+**Hypothesis:** Epigenetic regulation of gene expression through
+histone modification is involved in $\mathsf{CD4}^{+}$ T-cell
+activation and memory.
   
 ## Experimental design
 
@@ -205,6 +200,27 @@ Result:
 Data generated by Sarah Lamere, published in GEO as
 [GSE73214](https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE73214)
 
+## Time points capture phases of immune response
+
+\centering
+
+![](graphics/presentation/immune-response.png)<!-- { height=75% } -->
+
+## Why study these histone marks?
+
+::: incremental
+
+* **H3K4me3:** "activating" mark associated with active transcription
+
+* **H3K4me2:** Correlated with H3K4me3, hypothesized as a "poised" state
+
+* **H3K27me3:** "repressive" mark associated with inactive 
+
+* All 3 involved in T-cell differentiation, but activation dynamics
+  unexplored
+
+:::
+
 ## ChIP-seq sequences DNA bound to marked histones[^chipseq]
 
 \centering
@@ -213,10 +229,6 @@ Data generated by Sarah Lamere, published in GEO as
 
 [^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)
 
-## H3K4me2, H3K4me3, H3K27me3
-
-Why? <!-- TODO -->
-
 ## A few intermediate analysis steps are required
 
 ![Flowchart of workflow for data analysis](graphics/CD4-csaw/rulegraphs/rulegraph-all-RASTER100.png)