Place, date, unit, occasion etc. Slide 1 Molecular Immunology at IGM Who? Where? When? Why and What for? Gudrun Weiss.

Place, date, unit, occasion etc.Slide 1

Molecular Immunology at

IGM

Who? Where? When? Why and What for?

Gudrun Weiss


DTU KU LIFE

Where?

When?

5. floor at IGM at the end of “højhuset”

January 2009


Work Flow

Hanne Frøkiær

Continous Non Stop Process

Transformation Process1 Associate Professor

1 Post Doc

2 PhD Students

2 Lab Technicians

1 Lab Tech Trainee

Molecular Immunology Group


Molecular Immunology Group

Stine

Hanne

Louise

Kristina

Who?


The Real Engine of the Lab

Anni Shadi Marianne


PhD Student Kristina

Galathea Expedition

Marine Bacteria

Collaboration with DTU Aqua

Immune stimulatory effects?


Kristina's Winter 2010-11


Associate Professor Stine

DNA RNA Protein

miRNA (micro RNA)

Small non coding RNA

-- ug c ug a --------- u

au uua auc cuu guaaaggcgugu uug agg gu c gu c gaccguag u

ua aau uag gaa cauuucugcaca aac a5’

3’

Regulation of Biological Processes


PhD Student LouiseUptake of bacteria

in immune cells

Endocytosis


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


Why and What for?


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


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

MODE OF DELIVERY

INFANT NUTRITION (Breast or Formula

Feeding)

ANTIBIOTICS GENETIC FACTORS

MICROBIAL EXPOSURE DIETARY FACTORS

COMPOSITION OF THE

MICROBIOTA

MODE OF DELIVERY

INFANT NUTRITION (Breast or Formula

Feeding)

ANTIBIOTICS GENETIC FACTORS

MICROBIAL EXPOSURE DIETARY FACTORS

COMPOSITION OF THE

MICROBIOTA


- “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

Probiotics


Intestinal Tract


Dendritic Cells

Excretion of immunstimulatory factors

Immune response in the body


+ Growth factor

GM-CSF

Stimulation Assay

8 days: Immature Dendritic Cells

Proteins: Supernatant

• ELISA

Genes: Cells

• Real-Time PCR

• Microarray


How do Probiotic Bacteria stimulate the Immunsystem?

Up/Downregulation of Genes in Dendritic cells

Elucidation of Pathways

• Lactobacillus acidophilus

• Bifidobacterium bifidum


Lactobacilli

Bifidobacteria

Pro-inflammatory

Anti-inflammatory


Inhibition of pro-inflammatory interleukin IL-12- Lactobacillus Acidophilus

- Bifidobacterium Bifidum

Interleukin IL-12

0

0,5

1

1,5

2

2,5

3

3,5

4

4,5

0,1 1 10 20 40 60 80 100

Concentration of B. bifido Z9 (ug/ ml)

IL-1

2 (

ng

/ml)

ELISA

Proteins

Mechanisms?

MICROARRAY


L. acidophilus NCFM

Response to Virus

Microarray AnalysisScreening: >34.000 Genes


Activation of the Viral Immune System

Expression of the key regulator: Interferon β (IFN- β)

IFN-

0

1000

2000

3000Control

L. acidophilus NCFM

L. acidophilus X37

E. coli nissle 1917

B. bifidum Z9*Poly I:C

*

*

pg

/mL

Protection against influenza?!?


Lactobacillus acidophilus Virus + Pathogenic bacteria

JNKpathway

Mechanisms – Use of Knock Out Mice

?dsRNA ssRNA DNA


My Winter 2010-11


General Atmosphere

in the Lab?


Paper rejected


Paper accepted


Have a nice Weekend!!!

Any Questions???

Place, date, unit, occasion etc. Slide 1 Molecular Immunology at IGM Who? Where? When? Why and What for? Gudrun Weiss.

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