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Textbook Chem Bio- Bee Brainwashing - Chem 1AA3

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McMaster University
Pippa Lock

Brainwashing Bees, Drug Discovery and Aromaticity Bee Story  Homovanillyl Alcohol (HVA) – a component of Queen Mandibular Pheromone (QMP)  Queen Mandibular Pheromone (QMP) o Causes young workers to feed and groom queen o Suppresses new queens o Influences comb-building o Prevents workers ovaries from developing o Modulates development  Young bees exposed to QMP have altered dopamine in brains  Dopamine – neurotransmitter and hormone; required by insects for aversion learning (learning how to avoid unpleasant stimulus  Experiment (aversion learning): Exposed bees to odour then give electric shock o Normal bees – learn to try to sting as soon as they smell this specific odor o Bees exposed to QMP – did not learn to sting in response to the odour o Other components of QMP had no effect  QMP and HVA have no effect on appetitive learning (learning how to seek pleasant stimuli)  Experiment (appetitive learning): Bees exposed to odour then given sugar water o Normal bees – learn to extend proboscises in response to odour o Presence or absence of QMP or HVA have no effect on appetitive learning  HVA prevents young bees from forming bad memories, but does not affect ability to form pleasant memories  Other components of QMP are unpleasant to bees o High QMP concentrations repel worker bees and cause aggressive behaviour  High HVA levels in hive are associated with queen’s survival  Older bees (>15 days) that leave the hive to forage – unaffected by HVA o Aversion learning is important  Significance o Dopamine is a neurotransmitter in humans that is associated with learning – may give us insight into human memory and learning o Therapeutic Potential  Schizophrenia and other psychoses are associated with high dopamine levels – might be possible to treat diseases with an HVA-like molecule that selectively reduce dopamine in certain cells  Attention deficit disorder and Parkinson’s disease are both associated with low [dopamine] in parts of the brain Chemical Biology  For every new drug that appears on the market, a drug company has to synthesize and test ~5000 unsuccessful compounds  Challenges – convert a complex behavioural response into a quick chemical assay and to create a variety of HVA-like molecules o Assay – a measurement (as of compound or drug) to determine the presence, quantity or activity of one or more compounds High-Throughput Screening Dopamine Assay  Fast  Gives a colored product in the presence of dopamine  Measuring absorbance gives [dopamine] 1. Chemically derivatizing dopamine and covalently bonding it to the bottom of the well of a 96-well microtiter plate, then binding a dopamine-specific antibody to it 2. A second antibody, which binds to the first antibody, is added to the well 3. Second antibody is cross-linked to horseradish peroxidase (enzyme that produces colored product)  Amount of colored product is proportional to the amount of antibody present and therefore the amount of dopamine Cell-Based Assay  Using dopamine assay – screen bee neural cells to find ones that produce dopamine, but are inhibited by HVA  Once these cells are found – grow them in tissue culture  Can screen compounds for HVA-like activity 1. Grow dopamine-producing bee neural cells in tissue culture 2. The cells will produce dopamine, which will be dete
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