Future-Shaping Techologies

• Genetic Screening - Marfan Case• Gene Replacement - Bubble Babies• Stem Cells• Cloning - Dolly the Sheep• Agriculture - Crop Modification

SCID “Bubble” Baby

Dolly and Kid

Cloned Sheep

Stem Cells

Early embryonic cells can give rise to all cell types in the body

Embryonic cells can be used to create cell lines that can also differentiate into all cells in the body (Totipotent).

- These cells are called Embryonic Stem Cells (ES cells)

Stem cells divide to give rise to a copy of them selves and another cells that can differentiate into various cell types.

Stem Cells

Stem cells are also found in the adult body that have more limited potential to give rise to other cells (Pluripotent).

- Blood stem cells (replace red and white cells)- Neuronal stem cells (repair brain damage)

Potential Uses of Stem Cells:

- Generate pancreatic -cells: Treat diabetes- Generate red blood cells: Treat sickle cell anemia- Generate white blood cells: Treat B and T-cell leukemias- Generate all blood cells: Treat bubble babies- Generate heart or muscle cells: Repair heart/muscles- Generate neuronal cells: Repair neurological damage

- Reproductive stem cells (generate sperm and eggs)

A/P Axis

AbdomenHead

Tail

A possible picture of the most recent commonancestor of vertebrate and invertebrates

Mouth

Anus/Genitals

Nervous System

Non-neural Ectoderm

D/V Axis

Photosensitiveorgans

SensoryAppendages?

Eyespot?

Gills?

Protrusions orappendages

Human Disease Genes in Flies

• >3,100 of 5,000 Human disease genes identified

• Many disease genes have fly counterparts

– 75% disease genes related to a fly gene – 30% disease genes highly similar to a fly gene

• Disease genes with counterparts in flies fall into all major categories of disorders

Appropriate Disease Genes to Study in Flies

• Human Disease Gene Function Poorly Understood• Fly Counterpart Highly Related to Human Gene• Facility of Genetic Analysis in Fly• Identified Loci Subject to Explicit Test in Humans:

“Closing-the-Loop”

• Identify New Candidate Disease Genes– Alzheimer Disease (FAD)

• Identify Human Modifier Loci– Primary Congenital Glaucoma (PCG)

• Dissect Complex Polygenic Trait– Cardiac Defects in Down syndrome (DS)

• Place Disease Gene in a Pathway– Dyggve-Melchoir-Clausen syndrome (DMC)

• Identify Candidate Protein Targets– Angelman Syndrome (AS)

• Study host-pathogen interactions– Bacterial toxin function

Closing-the-Loop in Humans

Anthrax Toxins: Lethal Factor (LF) and Edema Factor (EF)

Anthrax Toxins: Lethal Factor (LF) and Edema Factor (EF)

- Do LF and EF act the same way in flies?- Are there new activities of LF or EF?- Is there evidence for synergy between LF and EF?

Anthrax Toxins: Lethal Factor (LF) and Edema Factor (EF)

EF Toxin

The fly wing as genetic assay system

BMP Pathway Mutant

L4L4

L5

L2

L3

Hh Pathway Mutant

L2

L3

L4

L5

L3

Normal Wing

L2

L4

L5

BMP

BMP

Hh

M Notch & Wg

Notch Pathway Mutant

L2

L3

L4

L5

Reduced hh functionL2

L3L4

L5

WTL2

L3

L4

L5

Hh determines the positions of the L3 and L4 Veins

Reduced hh function

dppAP

L3L4

hh dppEn

En -> Hh -> Diffuses ->dpp in A/P Organizer

ptc, dppAP En

L3

L4hh dpp

EF expression

LF and EF also have unexpected effects

LF expression

Synergy between LF and EF toxins

Wk-GAL4>EF

Wk-GAL4>LF+EF

Wk-GAL4>LF

Hes1 RT-PCR

UI WT pXO1 dLF dEF dLF/EF

HBMEC

PBS B.a LF B.a B.a EF B.a B.a

Infected with wt B. anthracis Infected with mutant B. anthracis lacking EF toxin

New CovenantJesse Bier

Nobody tells the flowers what to do,they grow the way they please.They don't take orders from me and you—nor do the grasses or trees.

But that was long ago,before the age of science.Now that we know what we know,we splice them to compliance.

Soon trees must do what they are told,according to special genes. Nothing the same as of old—and grasses, flowers know what that means.

Next to come are you and meafter the flowers, trees and grasses.But: Who will decide and overseenewfounded families, permanent classes?