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Where do new medicines come from?

Liu D - CBE Life Sci Educ (2011)

View Article: PubMed Central - PubMed

Affiliation: Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA. dliu@hhmi.org

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The research enterprise is confusing to most people, even for advanced students... How do results get transferred to medical advances? Toto talks about his research in his 2009 HHMI Holiday Lectures (www.hhmi.org/biointeractive/biodiversity/lectures.html) and has developed a website aimed at providing teachers and students with information about cone snails (www.theconesnail.com)... Currently a number of other peptide toxins derived from cone snails are in development to treat Parkinson's disease, epilepsy, heart disease, and pain... The animation found at www.hhmi.org/biointeractive/biodiversity/2009_prialt_blocks_motor.html shows the physiological action of ω-conotoxin... By the 1950s and 1960s, research had associated atherosclerosis with heart disease and established that artery-clogging plaques were composed largely of cholesterol... It was also known that HMG-CoA reductase was the rate-limiting enzyme on the path to making cholesterol... By the early 1970s, drug company employee Akira Endo was screening bacterial and fungal cultures to find inhibitors of HMG-CoA reductase... He soon found a candidate, the first member of the class now known as statins... They were also interested in the basic research problem of how insoluble cholesterol could be delivered to cells—“the delivery problem. ” I recommend visiting their Nobel Prize webpages and in particular reading the transcript of their Nobel lecture (http://nobelprize.org/nobel_prizes/medicine/laureates/1985/goldstein-lecture.html)... Brown and Goldstein discovered the answer to the delivery problem: Cells had receptors on their surface that bound cholesterol-rich LDL particles... Once separated from the LDL, the receptor could be recycled to the cell surface... The simple animation found on the W.H... Freeman website (http://bcs.whfreeman.com/thelifewire/content/chp05/0502003.html) illustrates endocytosis and recycling of LDL receptors, but not feedback regulation... Lowering the cholesterol content in liver cells could up-regulate LDL receptors, providing more receptors for taking LDL out of the bloodstream, thus lowering serum cholesterol levels and inhibiting plaque formation.

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Bacteria use a signaling system called quorum sensing (illustrated here by a frame from an HHMI animation) to coordinate aspects of their physiology and behavior, including turning on virulence factors.
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Figure 4: Bacteria use a signaling system called quorum sensing (illustrated here by a frame from an HHMI animation) to coordinate aspects of their physiology and behavior, including turning on virulence factors.

Mentions: An important aspect of the phenomena is that bacterial cells do not waste energy producing light during the day. So how do they turn light production on and off, how is it regulated, and what are the signals? It turns out that the answer is simply cycles of population growth. When bacteria multiply to a certain density, the community begins to produce light. The mechanism for this coordinated activity has come to have the catchy name “quorum sensing.” Bonnie Bassler, now at Princeton University, had heard about this fascinating symbiosis and as a microbiologist became particularly interested in understanding the genetics and biochemistry of light generation as well as the molecular signals for turning the lights on and off. Ultimately Bonnie turned to a free-living luminescent species of Vibrio bacteria that are easier to culture. You can view an animation of the signaling phenomena in action at www.hhmi.org/biointeractive/biodiversity/2009_QS_molecular_cascade.html (Figure 4) as well as a molecular animation of its genetic control at www.hhmi.org/biointeractive/biodiversity/2009_lux_operon_light_prod.html. As a budding scientist launching a career, Bonnie had challenges for those who dismissed bacterial light production as an interesting phenomenon not in the mainstream of biomedical research. The PBS program NOVA scienceNOW has an excellent video profile of Bonnie on its website (www.pbs.org/wgbh/nova/body/bonnie-bassler.html). Bonnie talks about the challenges, her good fortune, and her desire for her very basic research to lead to new drugs. In this regard, Bonnie has had good instincts and good fortune. It appears that quorum sensing is a universal phenomenon among bacteria of every species studied, including many important pathogenic species from Vibrio cholera to Salmonella and Escherichia coli. Most bacterial species use quorum-sensing signaling, not to coordinate light production, but to turn on virulence factors and coordinate attacks on their hosts when they have sufficient population. Bonnie presents her science at length in her iBioSeminars (www.ibioseminars.org/lectures/chemicalbiologybiophysics/besslar.html), in her Holiday Lectures (www.hhmi.org/biointeractive/biodiversity/lectures.html), and in an energetic 18-min TED talk that should appeal particularly to students (www.ted.com/talks/bonnie_bassler_on_how_bacteria_communicate.html).Figure 4.


Where do new medicines come from?

Liu D - CBE Life Sci Educ (2011)

Bacteria use a signaling system called quorum sensing (illustrated here by a frame from an HHMI animation) to coordinate aspects of their physiology and behavior, including turning on virulence factors.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3105917&req=5

Figure 4: Bacteria use a signaling system called quorum sensing (illustrated here by a frame from an HHMI animation) to coordinate aspects of their physiology and behavior, including turning on virulence factors.
Mentions: An important aspect of the phenomena is that bacterial cells do not waste energy producing light during the day. So how do they turn light production on and off, how is it regulated, and what are the signals? It turns out that the answer is simply cycles of population growth. When bacteria multiply to a certain density, the community begins to produce light. The mechanism for this coordinated activity has come to have the catchy name “quorum sensing.” Bonnie Bassler, now at Princeton University, had heard about this fascinating symbiosis and as a microbiologist became particularly interested in understanding the genetics and biochemistry of light generation as well as the molecular signals for turning the lights on and off. Ultimately Bonnie turned to a free-living luminescent species of Vibrio bacteria that are easier to culture. You can view an animation of the signaling phenomena in action at www.hhmi.org/biointeractive/biodiversity/2009_QS_molecular_cascade.html (Figure 4) as well as a molecular animation of its genetic control at www.hhmi.org/biointeractive/biodiversity/2009_lux_operon_light_prod.html. As a budding scientist launching a career, Bonnie had challenges for those who dismissed bacterial light production as an interesting phenomenon not in the mainstream of biomedical research. The PBS program NOVA scienceNOW has an excellent video profile of Bonnie on its website (www.pbs.org/wgbh/nova/body/bonnie-bassler.html). Bonnie talks about the challenges, her good fortune, and her desire for her very basic research to lead to new drugs. In this regard, Bonnie has had good instincts and good fortune. It appears that quorum sensing is a universal phenomenon among bacteria of every species studied, including many important pathogenic species from Vibrio cholera to Salmonella and Escherichia coli. Most bacterial species use quorum-sensing signaling, not to coordinate light production, but to turn on virulence factors and coordinate attacks on their hosts when they have sufficient population. Bonnie presents her science at length in her iBioSeminars (www.ibioseminars.org/lectures/chemicalbiologybiophysics/besslar.html), in her Holiday Lectures (www.hhmi.org/biointeractive/biodiversity/lectures.html), and in an energetic 18-min TED talk that should appeal particularly to students (www.ted.com/talks/bonnie_bassler_on_how_bacteria_communicate.html).Figure 4.

View Article: PubMed Central - PubMed

Affiliation: Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA. dliu@hhmi.org

AUTOMATICALLY GENERATED EXCERPT
Please rate it.

The research enterprise is confusing to most people, even for advanced students... How do results get transferred to medical advances? Toto talks about his research in his 2009 HHMI Holiday Lectures (www.hhmi.org/biointeractive/biodiversity/lectures.html) and has developed a website aimed at providing teachers and students with information about cone snails (www.theconesnail.com)... Currently a number of other peptide toxins derived from cone snails are in development to treat Parkinson's disease, epilepsy, heart disease, and pain... The animation found at www.hhmi.org/biointeractive/biodiversity/2009_prialt_blocks_motor.html shows the physiological action of ω-conotoxin... By the 1950s and 1960s, research had associated atherosclerosis with heart disease and established that artery-clogging plaques were composed largely of cholesterol... It was also known that HMG-CoA reductase was the rate-limiting enzyme on the path to making cholesterol... By the early 1970s, drug company employee Akira Endo was screening bacterial and fungal cultures to find inhibitors of HMG-CoA reductase... He soon found a candidate, the first member of the class now known as statins... They were also interested in the basic research problem of how insoluble cholesterol could be delivered to cells—“the delivery problem. ” I recommend visiting their Nobel Prize webpages and in particular reading the transcript of their Nobel lecture (http://nobelprize.org/nobel_prizes/medicine/laureates/1985/goldstein-lecture.html)... Brown and Goldstein discovered the answer to the delivery problem: Cells had receptors on their surface that bound cholesterol-rich LDL particles... Once separated from the LDL, the receptor could be recycled to the cell surface... The simple animation found on the W.H... Freeman website (http://bcs.whfreeman.com/thelifewire/content/chp05/0502003.html) illustrates endocytosis and recycling of LDL receptors, but not feedback regulation... Lowering the cholesterol content in liver cells could up-regulate LDL receptors, providing more receptors for taking LDL out of the bloodstream, thus lowering serum cholesterol levels and inhibiting plaque formation.

Show MeSH