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 2

DTU KU LIFE

Where?

When?

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

January 2009

Place, date, unit, occasion etc.Slide 3

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

Place, date, unit, occasion etc.Slide 4

Molecular Immunology Group

Stine

Hanne

Louise

Kristina

Who?

Place, date, unit, occasion etc.Slide 5

The Real Engine of the Lab

Anni Shadi Marianne

Place, date, unit, occasion etc.Slide 6

PhD Student Kristina

Galathea Expedition

Marine Bacteria

Collaboration with DTU Aqua

Immune stimulatory effects?

Place, date, unit, occasion etc.Slide 7

Kristina's Winter 2010-11

Place, date, unit, occasion etc.Slide 8

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

Place, date, unit, occasion etc.Slide 9

PhD Student LouiseUptake of bacteria

in immune cells

Endocytosis

Place, date, unit, occasion etc.Slide 10

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 11

Why and What for?

Place, date, unit, occasion etc.Slide 12

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

Place, date, unit, occasion etc.Slide 13

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

Place, date, unit, occasion etc.Slide 14

- “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

Place, date, unit, occasion etc.Slide 15

Intestinal Tract

Place, date, unit, occasion etc.Slide 16

Dendritic Cells

Excretion of immunstimulatory factors

Immune response in the body

Place, date, unit, occasion etc.Slide 17

+ Growth factor

GM-CSF

Stimulation Assay

8 days: Immature Dendritic Cells

Proteins: Supernatant

• ELISA

Genes: Cells

• Real-Time PCR

• Microarray

Place, date, unit, occasion etc.Slide 18

How do Probiotic Bacteria stimulate the Immunsystem?

Up/Downregulation of Genes in Dendritic cells

Elucidation of Pathways

• Lactobacillus acidophilus

• Bifidobacterium bifidum

Place, date, unit, occasion etc.Slide 19

Lactobacilli

Bifidobacteria

Pro-inflammatory

Anti-inflammatory

Place, date, unit, occasion etc.Slide 20

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

Place, date, unit, occasion etc.Slide 21

L. acidophilus NCFM

Response to Virus

Microarray AnalysisScreening: >34.000 Genes

Place, date, unit, occasion etc.Slide 22

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?!?

Place, date, unit, occasion etc.Slide 23

Lactobacillus acidophilus Virus + Pathogenic bacteria

JNKpathway

Mechanisms – Use of Knock Out Mice

?dsRNA ssRNA DNA

Place, date, unit, occasion etc.Slide 24

My Winter 2010-11

Place, date, unit, occasion etc.Slide 25

General Atmosphere

in the Lab?

Place, date, unit, occasion etc.Slide 26

Paper rejected

Place, date, unit, occasion etc.Slide 27

Paper accepted

Place, date, unit, occasion etc.Slide 28

Have a nice Weekend!!!

Any Questions???