September 20, 2011
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Three UCSF researchers have been named among the 2011 recipients of National Institutes of Health (NIH) Director's New Innovator Awards, one of the most competitively sought-after sources of research funding made available to young academic scientists through NIH. Each individual award covers up to $1.5 million in research costs over five years.
The three UCSF awardees are:
"The awards are intended to catalyze giant leaps forward for any area of biomedical research, allowing investigators to go in entirely new directions," said Dr. James M. Anderson, director of the Division of Program Coordination, Planning and Strategic Initiatives at the NIH.
According to the NIH, "Many new investigators have exceptionally innovative research ideas, but not the preliminary data required to fare well in the traditional NIH peer review system. As part of NIH's commitment to increasing opportunities for new scientists, it has created the NIH Director's New Innovator Award to support exceptionally creative new investigators who propose highly innovative projects that have the potential for unusually high impact."
Since inception, the NIH Director's Award Program has funded 216 New Innovator Awards since 2007, including the 49 new awards announced today.
The area of the frontal cortex of the brain responsible for speech production, called Broca's area after its discoverer, has been known since the mid-1800s, but it has been more than 70 years since major advances were made in understanding how our brain's microcircuitry organizes speech, according to Chang.
But Chang now will map and decode electrical signaling in this crucial brain region in detail for the first time. He will use closely spaced intra-cranial electrodes placed on the surface of Broca's region in brain surgery patients, as well as novel analytical methods to read out and map signaling activity by nerves. Working with bioengineering colleagues, Chang hopes to develop control over a neuro-prosthetic speech synthesizer for patients who cannot communicate due to severe paralysis. Results also will be applied to improve methods for preserving critical brain regions during surgery, he says.
The ability to speak that we take for granted from an early age depends upon exquisite motor control in the brain. Muscle movements in the lips, jaw, tongue and larynx are complexly and precisely orchestrated in time and place to produce all speech sounds. The techniques that Chang will use to map the brain circuitry that controls all these movements are more powerful than imaging techniques used previously, he says, because the high-resolution recordings are taken directly from the brain itself.
Huang is a pioneer in the development of "super-resolution" microscopy that goes beyond traditional limits of optical microscopes to allow the clear imaging of small structures within living cells for the first time.
He has been advancing a technique called Stochastic Optical Reconstruction Microscopy (STORM), which captures images of individual fluorescently labeled molecules within cells — and ultimately obtains images at a resolution more than ten times better than conventional fluorescence microscopy.
This technique is based on methods that randomly switch small fractions of labeled molecules to the fluorescent state and then determines their positions, while at the same time leaving most other molecules in the dark state.
Huang and others aim to further push the resolution of super-resolution microscopy to the scale of an individual protein molecule. They are particularly interested in understanding how protein molecules form large assemblies to perform coordinated functions inside a cell. These protein structures have been difficult to observe by other existing methods.
Barna is revolutionizing how scientists look at ribosomes, the molecular workhorses in the cell's protein-making factories.
Translating the genetic blueprint into the proteins that shape and enliven a fully realized organism means controlling where and when proteins get made. In studies of embryonic development Barna recently identified a major, previously unrecognized point of control over gene expression at the level of protein production. It is distinct from well-known modes of control — such as the switches governing gene activation or the small RNA molecules that silence gene expression.
The control involves a surprising new role for molecules that comprise the ribosome — called ribosomal proteins — recognized for decades only for their rote-like performance in helping to translate the genetic code. Barna, working with mice, has recently found that ribosomal proteins also discriminate among proteins and actively control the types of proteins that are made in particular types of cells — with repercussions for development and disease.
In fact, in recent years mutations in ribosomal proteins have been associated with unexpected human congenital abnormalities that lead to malformations of the spine, face, limbs, heart and other organs. Barna will continue to investigate how the ribosomes' newly identified function guides gene expression and normal embryonic development, research that also is likely to shed more light on human disease.
About UCSF Medical Center
UCSF Medical Center consistently ranks as one of the top 10 hospitals in the United States. Recognized for innovative treatments, advanced technology, collaboration among health care professionals and scientists, and a highly compassionate patient care team, UCSF Medical Center serves as the academic medical center of the University of California, San Francisco. The medical center's nationally preeminent programs include children's health, the brain and nervous system, organ transplantation, women's health and cancer. It operates as a self-supporting enterprise within UCSF and generates its own revenues to cover the operating costs of providing patient care.
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