Category Archives: Biochemistry

UTHSCT researchers receive five seed grants totaling $115,000

Five seed grants totaling $115,000 have been awarded to researchers at The University of Texas Health Science Center at Tyler. The locally raised money will help UTHSCT researchers explore new cures for serious diseases, saidSteven Idell, MD, Ph.D., UTHSCTs vice president for research.

Hong-Long Ji, Ph.D., associate professor of biochemistry, was awarded a $40,000 grant to study the relationship between abnormal genes and chronic obstructive pulmonary disease (COPD).

Usha Pendurthi, Ph.D., professor of molecular biology, received $40,000 to fund her work into how certain proteins that curb blood clotting affect the growth of cancerous tumors.

Proteins are required for the structure, function, and regulation of the bodys cells, tissues, and organs; each protein has unique functions. Hormones, enzymes, and antibodies are all examples of proteins.

Buka Samten, Ph.D., associate professor of microbiology and immunology, and Malini Madiraju, Ph.D., professor of biochemistry, were awarded $20,000 for preliminary research that could lead to a better vaccine against tuberculosis. Thats important, because TB kills more than a million people each year, according to the World Health Organization.

Anna Kurdowska, Ph.D., professor of biochemistry, received $10,000 for her research into a new way to treat acute lung injury, also known as acute respiratory distress syndrome (ARDS). And Amir Shams, Ph.D., associate professor of microbiology and immunology, received $5,000 to examine how to keep treatments for injured lungs inside those lungs.

These grants enable our scientists to pursue new and exciting research that could change our understanding of how serious diseases develop, as well as transform how we treat them. They help our researchers acquire the preliminary data they need to successfully compete for funding from the National Institutes of Health, the gold standard in biomedical research, Dr. Idell said, calling this years projects outstanding.

Funding for the seed grants comes from UTHSCs Research Council and the Texas Lung Injury Institute. Since 2002, scientists in the Center for Biomedical Research have been awarded $118.6 million in research dollars.

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UTHSCT researchers receive five seed grants totaling $115,000

LOS ANGELES Researchers at the UCLA stem cell center and the departments of chemistry and biochemistry and pathology and laboratory medicine have identified, for the first time, a generic way to correct mutations in human mitochondrial DNA by targeting corrective RNAs, a finding with implications for treating a host of mitochondrial diseases.

Mutations in the human mitochondrial genome are implicated in neuromuscular diseases, metabolic defects and aging. There currently are no methods to successfully repair or compensate for these mutations, said study co-senior author Dr. Michael Teitell, a professor of pathology and laboratory medicine and a researcher with the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA.

Between 1,000 and 4,000 children per year in the United States are born with a mitochondrial disease and up to one in 4,000 children in the U.S. will develop a mitochondrial disease by the age of 10, according to Mito Action, a nonprofit organization supporting research into mitochondrial diseases. In adults, many diseases of aging have been associated with defects of mitochondrial function, including diabetes, Parkinson's disease, heart disease, stroke, Alzheimer's disease and cancer.

"I think this is a finding that could change the field," Teitell said. "We've been looking to do this for a long time and we had a very reasoned approach, but some key steps were missing. Now we have developed this method and the next step is to show that what we can do in human cell lines with mutant mitochondria can translate into animal models and, ultimately, into humans."

The study appears today in the peer-reviewed journal Proceedings of the National Academy of Sciences.

The current study builds on previous work published in 2010 in the peer-reviewed journal Cell, in which Teitell, Carla Koehler, a professor of chemistry and biochemistry and a Broad stem cell research center scientist, and their team uncovered a role for an essential protein that acts to shuttle RNA into the mitochondria, the energy-producing "power plant" of a cell.

Mitochondria are described as cellular power plants because they generate most of the energy supply within a cell. In addition to supplying energy, mitochondria also are involved in a broad range of other cellular processes including signaling, differentiation, death, control of the cell cycle and growth.

The import of nucleus-encoded small RNAs into mitochondria is essential for the replication, transcription and translation of the mitochondrial genome, but the mechanisms that deliver RNA into mitochondria have remained poorly understood.

The study in Cell outlined a new role for a protein called polynucleotide phosphorylase (PNPASE) in regulating the import of RNA into mitochondria. Reducing the expression or output of PNPASE decreased RNA import, which impaired the processing of mitochondrial genome-encoded RNAs. Reduced RNA processing inhibited the translation of proteins required to maintain the mitochondrial electron transport chain that consumes oxygen during cell respiration to produce energy. With reduced PNPASE, unprocessed mitochondrial-encoded RNAs accumulated, protein translation was inhibited and energy production was compromised, leading to stalled cell growth.

The findings from the current study provide a form of gene therapy for mitochondria by compensating for mutations that cause a wide range of diseases, said study co-senior author Koehler.

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Repairing mutations in human mitochondria

Public release date: 12-Mar-2012 [ | E-mail | Share ]

Contact: Kim Irwin kirwin@mednet.ucla.edu 310-206-2805 University of California - Los Angeles Health Sciences

Researchers at the UCLA stem cell center and the departments of chemistry and biochemistry and pathology and laboratory medicine have identified, for the first time, a generic way to correct mutations in human mitochondrial DNA by targeting corrective RNAs, a finding with implications for treating a host of mitochondrial diseases.

Mutations in the human mitochondrial genome are implicated in neuromuscular diseases, metabolic defects and aging. There currently are no methods to successfully repair or compensate for these mutations, said study co-senior author Dr. Michael Teitell, a professor of pathology and laboratory medicine and a researcher with the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA.

Between 1,000 and 4,000 children per year in the United States are born with a mitochondrial disease and up to one in 4,000 children in the U.S. will develop a mitochondrial disease by the age of 10, according to Mito Action, a nonprofit organization supporting research into mitochondrial diseases. In adults, many diseases of aging have been associated with defects of mitochondrial function, including diabetes, Parkinson's disease, heart disease, stroke, Alzheimer's disease and cancer.

"I think this is a finding that could change the field," Teitell said. "We've been looking to do this for a long time and we had a very reasoned approach, but some key steps were missing. Now we have developed this method and the next step is to show that what we can do in human cell lines with mutant mitochondria can translate into animal models and, ultimately, into humans."

The study appears March 12, 2012 in the peer-reviewed journal Proceedings of the National Academy of Sciences.

The current study builds on previous work published in 2010 in the peer-reviewed journal Cell, in which Teitell, Carla Koehler, a professor of chemistry and biochemistry and a Broad Stem Cell Research Center scientist, and their team uncovered a role for an essential protein that acts to shuttle RNA into the mitochondria, the energy-producing "power plant" of a cell.

Mitochondria are described as cellular power plants because they generate most of the energy supply within a cell. In addition to supplying energy, mitochondria also are involved in a broad range of other cellular processes including signaling, differentiation, death, control of the cell cycle and growth.

The import of nucleus-encoded small RNAs into mitochondria is essential for the replication, transcription and translation of the mitochondrial genome, but the mechanisms that deliver RNA into mitochondria have remained poorly understood.

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Correcting human mitochondrial mutations

We bring you a guest post today from Faraz Hussain, who studies biochemistry at Illinois Institute of Technology. Faraz is a student of Joseph Orgel, the biologist researching preserved dinosaur tissue whom we profiled in the latest episode of Clever Apes. Here, Faraz introduces us to a completely different way of bridging the eons to bring dinosaurs into the present day. Gabriel Spitzer

Dinosaurs 180 million-odd year reign may be considered a lively old romp by most, but some clever apes would prefer to study these fossils in the flesh. One particular suborder, the theropods, never really went extinct at all. The birds that descended from them are the nearest living relatives today of both raptors and tyrannosaursperhaps none more so than the humble hen. Paleontologist Jack Horner, one of the most vocal exponents of avian dinosaurs being all around us, would rather that hens' more imposing ancestors had not evolutionarily "chickened out" in the first place.

Instead of messing about with amber-encased mosquitoes gorged on dino-DNA and playing fill-in-the-blanks with frog and bird genomes la Jurassic Park, Horner has been rallying his paleontologist pals and evolutionary developmental biologists to try a fresh tack on resurrecting a dinosaur: He wants to reverse-engineer a chickenosaurus. Hey, why start from scratch when you already have a fully-formed dinosaur in need of just a few minor genetic modifications? What follows is not your grandma's stuffed chicken recipe:

Chicken fingers:

While birds may have opted for wings instead of claws, both the T. rex and the chicken have only three digits at the end of each. In birds, however, these fingers have fused together. Hans Larsson at McGill University's Redpath Museum is looking for ways to short-circuit the genetic pathway responsible for this process in the chicken's embryonic stage and allowing the digits to separate so that, instead of those delicious wings, it ends up with far deadlier talons instead.

Rump:

A chicken has only a handful of vertebrae at the end of its spine that fuse to form what passes for its tail. In 2007, Larsson observed a tail in a developing chick embryo that had 16, although by the time it hatched these had dwindled to five. Turn off the genetic mechanism that triggers the breakdown and absorption of the tail, and voilyou're well on your way to the 40 or so vertebrae found in some of the heftiest hindquarters ever: the T. rex tail.

Teeth:

Matthew Harris discovered the rudiments of teeth on a frankenchicken embryo called the talpid2 usually known for its polydactyl fingers. While a far cry from the toothy old tyrannosaur grin that we know and lovethe genome of a chicken doesnt contain genes coding for enamel, nor can they produce dentin, which made up the bulk of those formidable fangsits finally a fighting chance for poultry to bite back!

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Clever Apes: Cooking up a dino-chicken

Renowned Scientist receives IRL Industry and Outreach Fellowship

IRL has appointed Professor Juliet Gerrard, a biochemist and leader in the industrial application of biochemistry in New Zealand as its second Industry and Outreach Fellow.

IRLs Industry and Outreach Fellowships have been established as part of IRLs drive to strengthen links between the research and high-value manufacturing organisations.

New Zealands economic success depends on our ability to get greater coordination and alignment across our research and industry sectors. One area of significant potential is through greater mobility of highly talented people, says Shaun Coffey, IRL Chief Executive.

The Industry and Outreach Fellowships attract leaders from the research sector into IRL to develop areas of scientific research and assist with their application to industry.

Professor Gerrard, who runs the Biomolecular Interaction Centre at the University of Canterbury, has held a number of significant positions in recognition of her scientific work and has recently been appointed Chair of the Marsden Council.

Professor Gerrard sees the overall strategic aim of the Industry and Outreach Fellowship programme as boosting collaboration.

"There is a lot of research being done in both universities and industry and Id like to bridge that gap between fundamental and applied work," she says. "By collaborating with IRL I believe that we will be able to achieve this."

Professor Gerards track record includes stints working for Crop and Food Research Ltd, and conducting research for the likes of Fonterra. She is also a principal investigator at the MacDiarmid Institute and Riddet Institute and has been on a number of editorial boards for scientific journals. She has written over 100 journal articles.

IRL Industry and Outreach Fellows are initially appointed for a five-year term and are mandated to resolve industry-related problems while building links between research institutions and business.

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Renowned Scientist receives IRL Industry and Outreach Fellow

In a report that appears online in the journal Structure, the BCM team describes the development of the semi-automated protocol that enables researchers to "rapidly generate an ensemble of initial models for individual proteins, which can later be optimized to produce full atomic models."

Taking the 3-D images generated through the process of electron cryo-microscopy and X-ray crystallography, the team developed this computational approach to produce these first-generation models of the proteins' structure or fold without prior knowledge of the protein's sequence or other information.

"This is important in working with big complexes made up of 10 to 30 proteins," said Dr. Matthew Baker, instructor in biochemistry and molecular biology at BCM and the paper's corresponding author. "You might know the structure of one or two proteins, but you want to know how all of those proteins interact with each other. As long as you can separate one protein from another, you can use this technique to make a model of each of the proteins in the complex."

"We borrowed from a classic computer science problem called the 'traveling salesman problem,'" said Dr. Mariah Baker, the paper's first author and a postdoctoral fellow at BCM. "It is in effect a connect-the-dots puzzle without the numbers."

In the traveling salesman problem, computer programmers are asked to figure the best route for a salesman who wants to visits all the cities where he sells just once while minimizing the distance traveled. Pathwalking solves a similar problem for proteins by looking for the optimal path through a 3-D image that connects C-alpha atoms, rather than cities, to form the protein's structure.

The tool is the answer to the dilemma presented by the near-atomic structures that are in the "middle" not of the highest resolution or the lowest resolution, said Matthew Baker.

As many as 25 percent of all structures imaged by electron cryo-microscopy and one-third of large protein complexes solved by X-ray crystallography are in the 3 to 10 angstroms range, said Matthew Baker.

Until now, the methodology used to annotate or trace the structure of protein from these density maps was usually tailored to specific cases, said Mariah Baker.

"They involved a lot of user intervention and the possibility to include bias," she said. That sparked a determination to automate the process with better routines that required less specific information.

"The question we asked was, can we trace a protein fold in a density map without a priori knowledge," she said. "The answer is that we can."

Continue reading here:
Semi-automated 'pathwalking' to build a protein model