Stories about: proteomics

News Notes: Pediatric science roundup

A quick look at recent research Vector finds noteworthy.

Tracking infants’ microbiomes

cute microbes-shutterstock_317080235-croppedMicrobiome studies are blooming as rapidly as bacteria in an immunocompromised host. But few studies have been done in children, whose microbiomes are actively forming and vulnerable to outside influences. Two studies in Science Translational Medicine on June 15 tracked infants’ gut microbiomes prospectively over time. The first, led by researchers at the Broad Institute and Massachusetts General Hospital, analyzed DNA from monthly stool samples from 39 Finnish infants, starting at 2 months of age. Over the next three years, 20 of the children received at least one course of antibiotics. Those who were repeatedly dosed had fewer “good” bacteria, including microbes important in training the immune system. Overall, their microbiomes were less diverse and less stable, and their gut microbes had more antibiotic resistance genes, some of which lingered even after antibiotic treatment. Delivery mode (cesarean vs. vaginal) also affected microbial diversity. A second study at NYU Langone Medical Center tracked 43 U.S. infants for two years and similarly found disturbances in microbiome development associated with antibiotic treatment, delivery by cesarean section and formula feeding versus breastfeeding.

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How amniotic and cerebrospinal fluids talk to the developing brain: proteomics

proteomics amniotic fluid cerebrospinal fluid brain development
Counterclockwise, from bottom left: In the earliest stage of nervous system development, the amniotic fluid is rich with proteins, shown as dots, that communicate with neural stem cells. As the neural tube closes and the brain takes shape, the proteins become fewer and less complex. (Hillary Mullan, Boston Children’s Hospital)

When we were developing in the womb, we were immersed in amniotic fluid. As our nervous systems formed, some of this fluid was trapped inside the neural tube, forming the cerebrospinal fluid that bathes our brains.

In the past, these fluids have been seen as a “cushion” or a place to dump waste products. But new research suggests that they actively participate in nervous system development.

Publishing this week in Developmental Cell, researchers led by Maria Lehtinen, PhD, and Kevin Chau in the Department of Pathology at Boston Children’s Hospital show that amniotic fluid and cerebrospinal fluid (CSF) contain rich portfolios of proteins that tell neural stem cells what to do — how to divide and what kinds of cells to make. They also show that the messages change in different phases of development.

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Proteomics provides new leads into nerve regeneration

Nerve regeneration. From Santiago Ramón y Cajal’s “Estudios sobre la degeneración y regeneración del sistema nervioso” (1913-14). Via Scholarpedia.

nerve regeneration proteomicsFirst in a two-part series on nerve regeneration. Read part 2

Researchers have tried for a century to get injured nerves in the brain and spinal cord to regenerate. Various combinations of growth-promoting and growth-inhibiting molecules have been found helpful, but results have often been hard to replicate. There have been some notable glimmers of hope in recent years, but the goal of regenerating a nerve fiber enough to wire up properly in the brain and actually function again has been largely elusive.

“The majority of axons still cannot regenerate,” says Zhigang He, PhD, a member of the F.M. Kirby Neurobiology Center at Boston Children’s Hospital. “This suggests we need to find additional molecules, additional mechanisms.”

Microarray analyses—which show what genes are transcribed (turned on) in injured nerves—have helped to some extent, but the plentiful leads they turn up are hard to analyze and often don’t pan out. The problem, says Judith Steen, PhD, who runs a proteomics lab at the Kirby Center, is that even when the genes are transcribed, the cell may not actually build the proteins they encode.

That’s where proteomics comes in. “By measuring proteins, you get a more direct, downstream readout of the system,” Steen says.

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The 98%: Proteomics reveals proteins made from ‘noncoding’ DNA

proteins and peptides from noncoding DNA
Probing the genome's 'dark side' could change our view of biology.
Vast chunks of our DNA—fully 98 percent of our genome—are considered “non-coding,” meaning that they’re not thought to carry instructions to make proteins. Yet we already know that this “junk DNA” isn’t completely filler. For example, some sequences are known to code for bits of RNA that act as switches, turning genes on and off.

New research led by Judith Steen, PhD, and Gabriel Kreiman PhD, of Boston Children’s Hospital’s Proteomics Center and Neurobiology program, goes much further in mapping this “dark side” of the genome.

In a report published last month in Nature Communications, they describe a variety of proteins and peptides (smaller chains of amino acids) arising from presumed non-coding DNA sequences. Since they looked in just one type of cell—neurons—these molecules may only be the tip of a large, unexplored iceberg and could change our understanding of biology and disease.

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Search for brain tumor biomarkers in urine strikes gold

Urine Vascular Biology Program netrin brain tumor biomarker Edward Smith Michael Klagsbrun

A good biomarker is one whose levels go up or down as a patient’s disease worsens or wanes. A great biomarker also gives key insights into disease development. A really great biomarker does both of these things and also serves as a treatment target.

With a protein called netrin-1, Edward Smith, MD, and Michael Klagsbrun, PhD, seem to have hit the trifecta. In a recent paper in Cancer Research, they report a clear relationship between urine netrin levels and medulloblastoma, the most common malignant brain tumor of children.

And show that netrin fuels the tumor’s invasion into healthy brain tissue.

And that blocking netrin may, at least in the laboratory, check the tumor’s spread.

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Fewer tests, lower costs …through urine?

(Harald/Flickr)
Lee’s team is using proteomics and glycomics to establish normal urine profiles, as well as biomarkers of kidney damage. (Harald/Flickr)

Part 1 of a two-part series on kidney disease. Part 2 is here.

In up to 5 percent of all pregnancies, children are born with some degree of kidney dilation or swelling, known as hydronephrosis. Unfortunately, says urologist Richard Lee, MD, of Boston Children’s Hospital, “many of these kids go through a lot of testing after birth and are followed for a long period of time—sometimes unnecessarily.”

Hoping to reduce such testing, Lee and his colleagues are turning to urine. They’ve been collecting comprehensive data on the urinary proteome—all the proteins urine normally contains. With this baseline information, they hope to establish biomarkers that identify kidney damage.

In a recently published study, Lee and his coauthors compared the urinary proteomes of healthy infant boys versus men to find out what happens naturally with age. Through their work, they identified nearly 1,600 protein groups and determined that the healthy male urinary proteome changes over time.

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Biomarkers for all

Just about any measurable molecule that changes with health and disease could be a biomarker. (David Guo's Master/Flickr)

Your doctor has a lot of tools to detect, diagnose and monitor disease: x-rays, MRIs, angiography, blood tests, biopsies…the list goes on.

What would be great would be the ability to test for disease in a way where there’s no or low pain (not invasive) and lots of gain (actionable data about the disease process itself, its progression and the success of treatment).

That’s where biomarkers come in.

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Ideas fly at Proteomics 2011

“What is proteomics?” Answering this simple question was the motivation for the Proteomics 2011, an annual symposium hosted by Judith and Hanno Steen of the Steen & Steen lab and The Proteomics Center at Children’s, featuring global innovators and local advances in proteomics at Children’s Hospital Boston, held last week. As a video at the start of the symposium showed, it’s a question that elicits a wide range of answers:


Video courtesy of the Carino Agency.

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Personalized rational medicine for all

Electrospray needle of a mass spectrometer

As a medical student at the last century’s end, I was taught to practice evidence-based medicine, to use the scientific method instead of the largely anecdotal, experiential practice of the physicians that came before. At this century’s beginning, medicine has begun yet another tectonic shift, termed personalized medicine.

Striving to use information about individual patients to their own benefit is probably as old as medicine itself.

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