Syndrome and RAG1 Nicholas Moehn Photo from http beyondessentialcomhealthyimmunesystem What is Omenn Syndrome httpshowyourhopecom20121104 httpenwikipediaorgwiki ID: 570930
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Slide1
Omenn Syndrome and RAG1
Nicholas Moehn
Photo from: http
://beyondessential.com/healthy-immune-system/Slide2
What is Omenn Syndrome?
http://showyourhope.com/2012/11/04/
http://en.wikipedia.org/wiki
/
Omenn_syndrome
#mediaviewer
/File:Omenn_syndrome.pngSlide3
What causes Omenn Syndrome?
RAG1Slide4
How does RAG1 work?Slide5
How well is RAG1 conserved?
99%
76%
59%
75%
90%
AA
AA
AA
AA
AA
AASlide6
Where is RAG1 mutated in OS?Slide7
What organisms contain RAG1?Slide8
A possible second player?Slide9
What causes Omenn Syndrome?Goal: To explore how AIRE and RAG1 contribute to the Omenn syndrome phenotypeHypothesis: Mutations in RAG1, in combination with deficiency in AIRE, creates the small, oligoclonal population of self-reactive immune cells present in individuals with Omenn
syndrome.Slide10
Aim 1: Determine if all individuals with Omenn syndrome are deficient for AIRE
RAG1
AIRE
Immunodeficiency
SCID
AIRE
RAG1
Omenn
Syndrome????Slide11
Approach: RNAseq
http://fcsanahuac.com/category/temas-selectos-de-ciencias-de-la-salud/Slide12
Aim 2: Identify mutations that would cause autoimmune symptomsRAG1
AIRESlide13
Approach: Next Gen SequencingSlide14
Aim 3: Demonstrate that deficiency in RAG1 and AIRE is sufficient to cause OS
RAG1
AIRE
Immunodeficiency
SCID
AIRE
RAG1
Omenn
Syndrome?Slide15
Approach: Crispr-Cas9 to create mutants
Crispr-Cas9
http://de.wikipedia.org/wiki/DurchflusszytometrieSlide16
Approach: Quantitative proteomics and cell counting
Cell countsSlide17
Future DirectionsTake advantage of the knowledge of AIRE mutation to try to develop a new treatment for patients with Omenn syndromeTo apply knowledge of Omenn syndrome to other SCIDs, immunodeficiencies, and autoimmune disease