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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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The Hawaiian bobtail squid has a symbiotic relationship with a bioluminescent bacterium.
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Figure 3: The Hawaiian bobtail squid has a symbiotic relationship with a bioluminescent bacterium.

Mentions: For conotoxin researchers, it's been a long journey from the reefs of the Indo-Pacific to new pharmaceutical treatments. Students are likely aware that there is a huge public health problem concerning antibiotic resistance, a perennial search for new antibiotics, and hopes for entirely new classes of antimicrobial agents. The next story has not reached the point of a new drug for patients yet but holds great promise. By sheer coincidence this story also features a predatory mollusk, the diminutive bobtail squid. Bobtail squid bury themselves during the day and come out at night to prey on crustaceans and fish. You can see videos of how they bury themselves on the vimeo website (vimeo.com/15490567) and on the Bioin teractive Biodiversity pages (www.hhmi.org/biointeractive/biodiversity/2009_bobtail_squid.html). These night hunters have a challenge when the moon is out. Moonlight causes them to cast a perceptible shadow as they cruise along the sandy shallows in search of prey. Their adaptation to this situation is to deploy a form of countershading by emitting luminance that they can tune to the amount of moonlight. They counter being silhouetted by the moon to avoid detection by the eyes of upward-glancing prey. The problem is that squid don't have the genes to directly produce light. Instead, they have evolved a symbiosis with Vibrio bacteria that can produce light. The Vibrio–squid symbiosis is a classic example of curiosity-driven basic research aimed at understanding life on our planet. Learn more about the symbiosis from two researchers at the University of Wisconsin in a feature at www.hhmi.org/biointeractive/biodiversity/Bioluminescence /01.html (Figure 3). Margaret McFall-Ngai and Ned Ruby have devoted their careers to understanding the squid–Vibrio symbiosis. Students at Davidson College have put together a website on bioluminescence that includes information on the symbiosis as well (www.bio.davidson.edu/people/midorcas/animalphysiology/websites/2005/plekon/index.htm). The Microbial Life Educational Resources pages also have information on the squid–Vibrio symbiosis (http://serc.carleton.edu/microbelife/topics/marinesymbiosis/squid-vibrio/collection.html), as do the Why Files webpages (http://whyfiles.org/2010/sustaining-symbiosis-new-clues).Figure 3.


Where do new medicines come from?

Liu D - CBE Life Sci Educ (2011)

The Hawaiian bobtail squid has a symbiotic relationship with a bioluminescent bacterium.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

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

Figure 3: The Hawaiian bobtail squid has a symbiotic relationship with a bioluminescent bacterium.
Mentions: For conotoxin researchers, it's been a long journey from the reefs of the Indo-Pacific to new pharmaceutical treatments. Students are likely aware that there is a huge public health problem concerning antibiotic resistance, a perennial search for new antibiotics, and hopes for entirely new classes of antimicrobial agents. The next story has not reached the point of a new drug for patients yet but holds great promise. By sheer coincidence this story also features a predatory mollusk, the diminutive bobtail squid. Bobtail squid bury themselves during the day and come out at night to prey on crustaceans and fish. You can see videos of how they bury themselves on the vimeo website (vimeo.com/15490567) and on the Bioin teractive Biodiversity pages (www.hhmi.org/biointeractive/biodiversity/2009_bobtail_squid.html). These night hunters have a challenge when the moon is out. Moonlight causes them to cast a perceptible shadow as they cruise along the sandy shallows in search of prey. Their adaptation to this situation is to deploy a form of countershading by emitting luminance that they can tune to the amount of moonlight. They counter being silhouetted by the moon to avoid detection by the eyes of upward-glancing prey. The problem is that squid don't have the genes to directly produce light. Instead, they have evolved a symbiosis with Vibrio bacteria that can produce light. The Vibrio–squid symbiosis is a classic example of curiosity-driven basic research aimed at understanding life on our planet. Learn more about the symbiosis from two researchers at the University of Wisconsin in a feature at www.hhmi.org/biointeractive/biodiversity/Bioluminescence /01.html (Figure 3). Margaret McFall-Ngai and Ned Ruby have devoted their careers to understanding the squid–Vibrio symbiosis. Students at Davidson College have put together a website on bioluminescence that includes information on the symbiosis as well (www.bio.davidson.edu/people/midorcas/animalphysiology/websites/2005/plekon/index.htm). The Microbial Life Educational Resources pages also have information on the squid–Vibrio symbiosis (http://serc.carleton.edu/microbelife/topics/marinesymbiosis/squid-vibrio/collection.html), as do the Why Files webpages (http://whyfiles.org/2010/sustaining-symbiosis-new-clues).Figure 3.

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