Download Molecular immunology at IGM

Molecular Immunology at
IGM
Who? Where? When?
Why and What for?
Gudrun Weiss
Place, date, unit, occasion etc.
Slide 1
Where?
When?
5. floor at IGM at the end of
“højhuset”
January 2009
DTU
Place, date, unit, occasion etc.
Slide 2
KU LIFE
Work Flow
Continous
Non Stop
Process
Hanne Frøkiær
Molecular Immunology Group
1 Associate Professor
1 Post Doc
2 PhD Students
2 Lab Technicians
date, unit,
occasion etc.
1 LabPlace,
Tech
Trainee
Slide 3
Transformation Process
Molecular Immunology Group
Stine
Who?
Hanne
Louise
Kristina
Place, date, unit, occasion etc.
Slide 4
The Real Engine of the Lab
Anni
Shadi
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Slide 5
Marianne
PhD Student Kristina
Galathea Expedition
Marine Bacteria
Collaboration with DTU Aqua
Immune
stimulatory
effects?
Place, date, unit, occasion etc.
Slide 6
Kristina's Winter 2010-11
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Slide 7
Associate Professor Stine
DNA
RNA
Protein
miRNA (micro RNA)
Small non coding RNA
5’ -- ug
c ug a
--------u
ua aau uag gaa cauuucugcaca
aac a
au uua auc cuu guaaaggcgugu
uug a
c gu c
gaccguag
u
3’ gg gu
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Slide 8
Regulation
of
Biological
Processes
PhD Student Louise
Uptake of bacteria
in immune cells
Endocytosis
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Slide 9
Research Topic:
Immunological Recognition and
Response to Microorganisms
• How are Microorganisms recognized?
• Which Cells interact with Microbes?
• What determines the Response to Microbes?
• How is a Microbe recognized as a Pathogen?
Special Focus: Gastro-Intestinal Tract
Place, date, unit, occasion etc.
Slide 10
Why and What for?
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Slide 11
The Gastrointestinal Tract
• One of the key organs in the body
• Large surface area: 150 - 200 m2
(skin: only 2 m2)
• Surface small intestine:
Size of a Tennis Court
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Slide 12
The Human Microbiota
Human Gastro-Intestinal Tract
~ 1x1014 bacteria, several thousand different species
• 10 x more bacteria cells than human cells
• 100 x more bacteria genes than human genes
INFANT NUTRITION
(Breast or Formula
Feeding)
MODE OF
DELIVERY
ANTIBIOTICS
COMPOSITION
OF THE
MICROBIOTA
MICROBIAL EXPOSURE
Place, date, unit, occasion etc.
Slide 13
GENETIC FACTORS
DIETARY FACTORS
Probiotics
- “Pro Bio” – “For life”
- Gram positive Lactic Acid Bacteria
- Lactobacilli
- Bifidobacteria
-
Natural inhabitants of the intestine, “Friendly Bacteria”
-
Beneficial Effects: Infectious diarrhea (especially rotavirus)
Inflammatory bowel disease, Lactose intolerance, Allergies
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Slide 14
Intestinal Tract
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Slide 15
Dendritic Cells
Excretion of
immunstimulatory
factors
Immune response in
the body
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Slide 16
Stimulation Assay
+ Growth factor
GM-CSF
8 days: Immature
Dendritic
Cells
Proteins: Supernatant
Genes: Cells
• ELISA
• Real-Time PCR
Place, date, unit, occasion etc.
Slide 17
• Microarray
How do Probiotic Bacteria
stimulate the Immunsystem?
• Lactobacillus acidophilus
• Bifidobacterium bifidum
Up/Downregulation of
Genes in Dendritic cells
Elucidation of
Pathways
Place, date, unit, occasion etc.
Slide 18
Pro-inflammatory
Lactobacilli
Bifidobacteria
Place, date, unit, occasion etc.
Slide 19
Anti-inflammatory
Inhibition of pro-inflammatory interleukin IL-12
- Lactobacillus Acidophilus
- Bifidobacterium Bifidum
Interleukin IL-12
4,5
Mechanisms?
4
3,5
Proteins
IL-12 (ng/ml)
ELISA
MICROARRAY
3
2,5
2
1,5
1
0,5
0
0,1
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Slide 20
1
10
20
40
60
Concentration of B. bifido Z9 (ug/ml)
80
100
Microarray Analysis
L. acidophilus NCFM
Screening:
>34.000 Genes
Response to Virus
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Slide 21
Activation of the Viral Immune System
Expression of the key regulator: Interferon β (IFN- β)
IFN-
*
3000
pg/mL
2000
*
*
1000
Control
L. acidophilus NCFM
L. acidophilus X37
E. coli nissle 1917
B. bifidum Z9
Poly I:C
0
Protection against influenza?!?
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Slide 22
Mechanisms – Use of Knock Out Mice
Lactobacillus acidophilus
Virus + Pathogenic bacteria
dsRNA
ssRNA
DNA
?
JNK
pathway
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Slide 23
My Winter 2010-11
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Slide 24
General
Atmosphere
in the Lab?
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Slide 25
Paper rejected 
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Slide 26
Paper accepted 
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Slide 27
Have a nice
Weekend!!!
Any Questions???
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Slide 28