future-shaping techologies genetic screening - marfan case gene replacement - bubble babies stem...
Post on 20-Jan-2016
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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?