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- Introduction
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1. Drosophila genetics - the first 25 years
- Prof. Dan Lindsley
- Establishment of the Primary Body Axes
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2. Homeotic genes in Drosophila's bithorax complex - The legacy of Ed Lewis
- Prof. Francois Karch
- Cell Type Specification and Organ Systems
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4. From germ cell specification to gonad formation
- Prof. Ruth Lehmann
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5. Drosophila stem cells
- Prof. Michael Buszczak
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6. Legacy of drosophila genetics: female germline stem cells
- Prof. Michael Buszczak
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7. Intestinal stem cell-mediated repair in Drosophila 1
- Prof. Tony Ip
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8. Intestinal stem cell-mediated repair in Drosophila 2
- Prof. Tony Ip
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10. Axon guidance in Drosophila
- Prof. John Thomas
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11. Development and physiology of the heart
- Prof. Rolf Bodmer
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12. Identification of host defenses in the Drosophila gut using genome-scale RNAi
- Prof. Dominique Ferrandon
- Genome Organization and Function
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13. The genetic analysis of meiosis in Drosophila melanogaster females
- Prof. R. Scott Hawley
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15. Dorsal-ventral patterning of the Drosophila embryo
- Prof. Mike Levine
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17. Genome-wide pooled CRISPR screen in arthropod cells
- Prof. Norbert Perrimon
- Behavior
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19. Genetics of chemosensory transduction: taste and smell
- Dr. Leslie Vosshall
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20. Cracking the case of circadian rhythms by Drosophila genetics
- Prof. Jeffrey C. Hall
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21. Sleep in Drosophila
- Dr. Ralph Greenspan
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23. Drosophila as a model for drug addiction
- Prof. Ulrike Heberlein
- Mechanism of Human Disease
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24. Cross-genomic analysis of human disease genes
- Prof. Ethan Bier
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25. Human neurodegenerative disease: insights from Drosophila genetics
- Prof. Nancy Bonini
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26. Metastasis of Drosophila tumors
- Prof. Allen Shearn
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27. Rac-enhanced CAR immunotherapy: RaceCAR
- Prof. Denise Montell
- Evolution of Adaptive Novelties
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29. The evolution of morphological novelty
- Prof. Nipam Patel
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30. The genetic architecture of complex traits: lessons from Drosophila
- Prof. Trudy Mackay
- Archived Lectures *These may not cover the latest advances in the field
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31. Using gene expression information to provide insights into patterning and differentiation
- Prof. Angelike Stathopoulos
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32. Regulation of gastrulation in Drosophila
- Prof. Dr. Maria Leptin
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33. microRNA function in stem cells
- Prof. Hannele Ruohola-Baker
Printable Handouts
Navigable Slide Index
- Introduction
- Why drugs?
- Why Drosophila?
- Ethanol - a non specific drug
- A quote by M. Ashburner
- Models of addiction
- The approach
- What do ethanol-exposed flies do?
- A really drunk fly
- The inebriometer
- Identification of important mutants and genes
- The genetic screen process (1)
- Cheapdate flies are sensitive in the inebriometer
- Absorption and metabolism of cheapdate flies
- Cheapdate is a mutation in amnesiac
- Amnesiac rescues cheapdate's ethanol sensitivity
- Drosophila mutants in cAMP signal transduction
- The unbearable likeness of beings
- Targeting NS disruptions
- Regulation of ethanol snsitivity by PKA activity
- GAL4/UAS system
- Genetic manipulation of PKA activity
- Reduced activity with PKA inhibitor expression
- Acute PKA inhibition increases ethanol sensitivity
- Use of a collection of GAL4 lines
- P[GAL4] x UAS-lacZ
- Brain expression of P[GAL4], line 201Y (1)
- MB ablation does not alter ethanol sensitivity
- Brain expression of P[GAL4], line 201Y (2)
- PI cells express insulin-like peptides (dILPs)
- Effect of PKA inhibition in IPCs
- PI neurons project to the ring gland
- The insulin receptor (INR) signaling pathway
- Reduced dINR function increases EtOH sensitivity
- Role of INR pathway in ethanol sensitivity
- PI3K inhibition increases EtOH sensitivity
- Expression of constituitivley active hFOXO
- The insulin receptor (INR) signaling pathway
- Insulin pathway and ethanol's rewarding effects
- Mechanisms in fly's responses to cocaine
- Psychostimulant exposure and behavioral analysis
- Mock exposure
- Acute cocaine exposure
- A simple behavioral assay
- Cocaine dose-response
- Mechanism of cocaine action
- Effect of dopamine depletion
- The genetic screen process (2)
- Effect of dLmo mutations on cocaine sensitivity
- Lmo genomic region
- How does dLMO work?
- Where does dLmo function?
- GAL4 expression in varios CNS patterns
- Mapping the dLmo site of action
- dLmo-GAL4 expression in PDF-positive cells
- What is known about LNvs?
- Does dLmo regulate cocaine sensitivity?
- Two possible models for dLmo and LNvs function
- Role of LNvs in cocaine sensitivity
- The Working model
- Summary
- The Drosophila model and human drug addiction
- Thank you
Topics Covered
- Behaviors induced by ethanol and cocaine in Drosophila
- Genes and pathways that regulate ethanol-induced behaviors: amnesiac, and the cAMP/PKA and insulin pathways
- Genes and neurons that regulate cocaine-induced behaviors: dlmo and the PDF-producing lateral neurons
Links
Series:
Categories:
Therapeutic Areas:
Talk Citation
Heberlein, U. (2017, September 25). Drosophila as a model for drug addiction [Video file]. In The Biomedical & Life Sciences Collection, Henry Stewart Talks. Retrieved December 21, 2024, from https://doi.org/10.69645/PGZX7987.Export Citation (RIS)
Publication History
Financial Disclosures
- Prof. Ulrike Heberlein has not informed HSTalks of any commercial/financial relationship that it is appropriate to disclose.
Drosophila as a model for drug addiction
A selection of talks on Neurology
Transcript
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0:00
Drosophila as a model for drug addiction,
Ulrike Heberlein Department of Anatomy,
University of California at San Francisco.
0:10
Drug addiction and drug abuse are major
problems in medicine and society.
The Center for Disease Control recently
reported that in the year 2000, over half
a million people died in the United States
as a consequence of excessive drug use.
Despite the immensity of the problem,
few treatment strategies
are currently available and those that
exist have met with limited success.
The reasons for this are multi-faceted.
First, drug addiction is still not
broadly acknowledged as a disease and
the associated stigma has
hampered human studies.
Second, while it is well
established that genetic and
environmental factors contribute to an
increased risk for addiction, the genetic
factors are quite complex and have so
far eluded definitive identification.
Finally, while the primary sites of
action of many abuse drugs are known,
little is known about the cellular and
molecular mechanisms by which drug use
changes the brain into the addicted state.
1:11
Drosophila was introduced in the mid
1990s as a model system to help define
the mechanisms by which abuse drugs act in
the nervous system to alter behavior and
the mechanisms by which the brain
changes upon repeated drug exposure.
The approach relied on 2 main assumptions.
1st, that the mechanisms by which genes
regulate drug induced behaviors would be
conserved in evolution.
In that lessons learned in flies would
therefore be applicable to mammals,
including humans and 2nd that by studying
some relatively simple behaviors such as
acute drug responses,
something would be learned about the much
more complex process of addiction.
Flies provide of course, economy of scale,
the benefit of about 100 years
of classical genetics and several
decades of molecular genetic analysis.
They have a sequence genome and
have shown a substantial degree of
functional conservation with mammals.
Place had a complex nervous system in are
capable of many sophisticated behaviors.
They have been and continue to be
an extremely successful model system in
behavioral genetics where they have helped
decipher the basis of circadian rhythms,
learning and memory, and
courtship, among others.