Dr. James E. Metherall

James Metherall, Ph.D. - Assistant Professor, Department of Human Genetics, University of Utah - $275,894 award (3-year grant from 8/95 - 7/98)TITLE: "Genetic Defects in Proteins Required for Intracellular Cholesterol Transport Cause NP-C"

James Metherall, Ph.D. - Assistant Professor, Department of Human Genetics, University of Utah - $275,894 award (3-year grant from 8/95 - 7/98)TITLE: "Genetic Defects in Proteins Required for Intracellular Cholesterol Transport Cause NP-C"

The major significance of the new paper, says James E. Metherall, associate professor of human genetics at the University of Utah, "is that the beauveriolides don't seem to cause the same side effects as other ACAT inhibitors," including diarrhea and kidney tissue damage in mouse models."This suggests that the side effects are not due to direct inhibition of ACAT" and that it might be possible to modify existing ACAT inhibitors to eliminate the side effects, Metherall says.

James Metherall, Ph.D. Associate Professor, Genetics

Dr. James Metherall (University of Utah) presented some of his own work on the search for the SLO/RSH gene among the genes for a group of proteins that serve to move cholesterol within cells.Once these investigators have the SLO/RSH gene in hand, many new avenues of SLO/RSH research will open.

The basics of cholesterol biochemistry in SLO/RSH syndrome was another major focus of the meeting.Some of the topic discussed included sterol chemistry in cultured cells (Dr. Sankhavarum Panini, Roosevelt Institute, Denver), cholesterol metabolism in the brain (Dr. Pierre Morell, University of North Carolina; and Dr. William Conner, Oregon Health Sciences University), and cholesterol transport in cells (Dr. Metherall) Drs.

COURTESY OF JIM METHERALL

Jim Metherall, associate professor of genetics at the University of Utah, got his first robot in the mid-1990s while buried by a project on cholesterol homeostasis."We were trying to clone a gene by complementing a mutation in mammalian cells, and we couldn't do it with an entire cDNA library, because the signal-to-noise was too low," Metherall explains.So he broke the library into small pools, isolated DNA, and then tested each pool for activity. A few thousand minipreps later, Metherall recalls, "A very qualified, capable, valuable technician approached me and said she was sick of it.It was either automate or find new personnel."Metherall applied for and won an onsite equipment competition grant, some $50,000 to $60,000, as he recalls, which went into a BioMek 2000 automated liquid handler (about $45,000 at the time) and accessory equipment such as a plate washer and pump. Today, he still uses the handler, though it's part of a much larger system, including microplate hotels, PCR machines, a microarray spotter, a scintillation counter, and a spectrophotometer, all linked by two robotic arms.The entire assembly occupies 100 square meters of lab space.And with only four members (not counting collaborators), Metherall's group is smaller than what you might expect for a robotics-hub at the University of Utah. Ten years in the making, Metherall's robot is well beyond the scope of what most researchers would need starting out.But if you've been wondering if automation is right for you, consider these five questions:

1. Is your workload big enough?Metherall's technician ran thousands of preps by hand before the lab acquired a robot, which eventually would run another 5,000 preps or so before that particular project ended.
...
On the other hand, says Metherall, some processes are so difficult and expensive, automation makes sense even without industrial-scale throughput.
...
Frederick turned to Metherall.
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Some guidelines from the experts: "Go with a highly flexible, modular design," says Metherall."Your project will end at some point, and the equipment will be obsolete if it's highly specialized." Metherall's robot, for instance, has been used for several applications, including genome-wide gene-expression analysis of Drosophila embryos; handling whole-genome RNAi libraries in Caenorhabditis elegans; Frederick's synthetic genetic arrays in yeast; and kinase screens."You started with minipreps but you could end up doing kinase screens, expression screens - just a wide range of things if you concentrate on flexibility," he says.

COURTESY OF JIM METHERALL

Jim Metherall, associate professor of genetics at the University of Utah, got his first robot in the mid-1990s while buried by a project on cholesterol homeostasis."We were trying to clone a gene by complementing a mutation in mammalian cells, and we couldn't do it with an entire cDNA library, because the signal-to-noise was too low," Metherall explains.So he broke the library into small pools, isolated DNA, and then tested each pool for activity. A few thousand minipreps later, Metherall recalls, "A very qualified, capable, valuable technician approached me and said she was sick of it.It was either automate or find new personnel."Metherall applied for and won an onsite equipment competition grant, some $50,000 to $60,000, as he recalls, which went into a BioMek 2000 automated liquid handler (about $45,000 at the time) and accessory equipment such as a plate washer and pump. Today, he still uses the handler, though it's part of a much larger system, including microplate hotels, PCR machines, a microarray spotter, a scintillation counter, and a spectrophotometer, all linked by two robotic arms.The entire assembly occupies 100 square meters of lab space.And with only four members (not counting collaborators), Metherall's group is smaller than what you might expect for a robotics-hub at the University of Utah.
...
On the other hand, says Metherall, some processes are so difficult and expensive, automation makes sense even without industrial-scale throughput.
...
Frederick turned to Metherall.
...
Some guidelines from the experts: "Go with a highly flexible, modular design," says Metherall."Your project will end at some point, and the equipment will be obsolete if it's highly specialized." Metherall's robot, for instance, has been used for several applications, including genome-wide gene-expression analysis of Drosophila embryos; handling whole-genome RNAi libraries in Caenorhabditis elegans; Frederick's synthetic genetic arrays in yeast; and kinase screens."You started with minipreps but you could end up doing kinase screens, expression screens - just a wide range of things if you concentrate on flexibility," he says.