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The Michael and Kate Barany Award for Young Investigators recognizes an outstanding contribution to biophysics by a person who has not yet achieved the rank of full professor at the time of nomination.

Sabeeha received the award "in recognition of her research on the role of metals in regulating the biosynthesis and assembly of metalloproteins in photosynthetic eukaryotes. Her innovative investigations established the critical role of trace metals as reglatory agents in the biogenesis and accumulation of electron transport components required for the functional photosynthetic apparatus and provided new insights into the molecular mechansims underlying these fundamental processes." The award was presented this past summer at Plant Biology '99, the Society's annual meeting.

The American Society for Cell Biology will present the award to Ray at its annual meeting in December at the Convention Center in Washington, D.C. Ray is being recognized for his "outstanding contribution to the cell cycle field using biochemical and genetic approaches in the yeast S. cerevisiae to dissect the mechanisms of the G1-S transition and the exit from mitosis."

We found the following article in the Nation section of the Baltimore Sun on November 26, 1999.

Freeze Frame Microscope Could Demystify Cancer

California University says laboratory tool "surprises" mutant cells

ORANGE COUNTY REGISTER

IRVINE, Calif.---The first microscope that can penetrate the mysteries of living human cells has been built by University of California-Irvine researchers, with the possibility it will eventually change the way diseases like cancer are diagnosed and treated.

The technology uses shock waves produced by laser beams to capture, freeze, and chemically analyze the contents of a cell. The ability to surprise a cell before it has time to change its internal chemistry in defense is a key factor to learning how diseased cells behave, and what types of drugs might treat them best.

"We've had so much interest in what we're doing that we're going to try to accelerate the program," said Dr. Michael Berns, director of the Beckman Laser institute at UCI, which received $2.2 million from the National Institutes of Health last month. The grant will be used to develop a miniaturized commercial prototype of the microscope over the next few years. Researchers hope that eventually hospitals and medical labs will use the technology to study the chemistry inside the living cells of sick people in the same way that blood tests are given today.

"(Berns) is proposing a major breakthrough in our capacity to understand what happens in diseased cells," said Dr. Michael Morron, director of biomedical technology for the National Center for Research Resources. "The hope is to try to distinguish what makes cancer cells go bad."

The idea started two years ago with Dr. Nancy Allbritton, a UCI medical researcher studying how cancer cells behave. Like many scientists, Allbritton was frustrated with her inability to study the internal processes of cells, which are the building blocks of the human body. Cancer begins when normal cells start reproducing wildly. No one knows why they do this, but researchers like Allbritton hope that learning what triggeers this erratic behavior in a cell can teach them how to turn it off.

Today, the most common way of analyzing cellular chemistry is to take millions of cells, put them in a blender, and then study the chemicals that are left. But this doesn't tell scientists how living cells actually perform.

The difficulty is that cells are so small: a billionth of a millimeter in size. [Actually cells are much bigger than that....more like a hundredth of a millimeter in size.--D.F.] Each is surrounded by a plasma membrane; inside are tens of thousands of molecules, each with their own chemistry.

Scientists have figured out how to get inside that plasma membrane---using detergent to dissolve it, for example---but not without dramatically altering the cell's composition.

"It's pretty difficult to analyze a very tiny speck that you can barely see under the microscope and figure out how all these tens of thousands of molecules are interacting with each other," said Bruce Tromberg, director of Beckman's biotechnology resource center. "But those cells are determining how long you are going to live and how you are going to fight disease."

At lunch in 1997, Allbritton confided her frustration to Tromberg. He responded that laser techology at the Beckman Institute could probably help. Within months, the pair had come up with a system that uses focused bursts of light to expode a cell within 30 milliseconds --- so fast that it doesn't have time to react defensively. Then, the chemical contents of the cell are transferred into a micropipette ---a glass tube ---where its molecules are electrically sorted and measured by computer. "The cell is alive until the moment we do this," Allbritton said. "We do it so fast, we freeze all the reactions."

After the success of the technology, UCI applied for a patent and for a federal grant to expand its capabilities. Now, the college wants to share. If Berns and his team of scientists working jointly from several UCI departments succeed in their goal of building a miniature computer microchip with the laser information embedded in it, it could be developed by a manufacturing company and marketed world-wide.

Most immediately, Allbritton, her husband, Chris Sims, who is also a member of the team, and four others are studying how tumor cells react while working on a version of the miscoscope that can be placed on a device only a few inches square. "The idea is to develop systems to fit onto a small glass or plastic device that is easily transportable," Sims said. "Then, everybody could have it in their lab to analyze cells."

Ka Yee received this five-year, $625,000 award to further support her biophysical and biochemical research on lung sufractant, a complex of lipids and proteins that keeps the lungs from collapsing, and to support her work on beta-amyloid, the substance implicated in death of brain cells in Alzheimer's Disease.

Phyllis was one of five young scientists to receive awards in the first year of an experimental five-year program begun by the W.M. Keck Foundation.

Rheza received the award for building molecules that help reveal the nature of living systems. His team was the first to describe a self-replicating polypeptide, a short protein that can make copies of itself, through a process known as autocatalysis.

Elaine, 1981 Searle Scholar and more recently Chair of the Advisory Board, was named President-elect of the ASCB. She takes office in January of 2000 and will serve as President for the year 2001.

Ernest G. Peralta
Associate Professor
Department of Biochemistry & Molecular Biology
Harvard University

It is with deep sadness that we report Ernie's death on May 17 from glioblastoma. Ernie was able to keep his research program going quite productively until his death. The lab is continuing the research, some of it under the mentorship of new Searle Scholar, Catherine Dulac, whose lab is nearest neighbor to Ernie's. Lily Jan and David Julius and James Lechleiter wrote the following testimonial for the Searle website:

With a long-standing interest in determining how muscarinic acetylcholine receptors modulate cardiac and smooth muscle function, exocrine secretion, and central neuronal activities important for learning and memory, Dr. Ernie Peralta pioneered the molecular studies that led the field into fascinating and uncharted territories. By his own account, Ernie was a reductionist whose approach to understanding a biological signaling pathway involved first identifying key molecular components of the system through gene cloning methods. These molecules were elegantly manipulated in "simple" heterologous expression systems with the aim of understanding how they interact to regulate interesting and fundamental physiological processes, such as neurotransmitter release at the synapse or pacemaker activity in the heart.

As a postdoctoral fellow at Genentech, Ernie helped to usher in a new and exciting era of molecular pharmacology by isolating cDNA clones encoding muscarinic acetylcholine receptors. Indeed, this work represents one of the earliest success stories in identifying a gene encoding a G protein-coupled receptor and examining its properties in heterologous expression systems. Ernie made great use of these clones by demonstrating that a single transmitter or hormone can modulate different second messenger signaling pathways, and that specificity is determined by the complement of receptor and G protein subtypes that a cell expresses. While this may seem obvious from today's perspective, Ernie's studies were among the first to establish a logical molecular framework for understanding how G protein-coupled receptors "talk" to specific G proteins and route their signals to a given second messenger signaling pathway.

Ernie's molecular analyses of the cloned muscarinic receptors revealed that inhibitory acetylcholine actions are mediated by the m2 and m4 receptors coupled to pertussis toxin-sensitive G proteins, whereas excitatory actions are mediated by m1, m3 and m5 receptors coupled to Gq/11 proteins and the phospholipase C pathway.

Following molecular characterization of the muscarinic acetylcholine receptors, Ernie's group went on to examine mechanisms underlying the inhibitory as well as the excitatory pathways. Their novel findings concerning the inhibitory pathways include molecular analysis of muscarinic potassium channel activation by the G protein beta-gamma subunits and biochemical studies of the function of the regulators of G protein signaling (RGS). In both cases, the studies were original and highly influential.

Of equal and perhaps even greater impact were the many discoveries of Ernie's group regarding mechanisms mediating the excitatory pathways. The unexpected finding of tyrosine kinase-mediated Kv1.2 potassium channel suppression by m1 receptor in neuroblastoma-glioma cells as well as expression systems received wide attention, pointing to connections between signaling pathways previously thought to be separate. Characteristic of Ernie's insightful and rigorous scientific style, his group pursued the underlying mechanisms to reveal a number of surprises. The uncovered novel effects of m1 receptor activation include ligand-independent EGF receptor activation, Pyk2 tyrosine kinase stimulation, Kv1.2 channel regulation via physical association with the small GTPase RhoA, and tyrosine phosphorylation-dependent association between the channel and receptor tyrosine phosphatase which in turn terminates channel suppression by m1 receptor.

In addition to the truly original and valuable leads that these studies have provided to the signaling field, the specific findings on m1 modulation of Kv1.2 channels will have major impact on our understanding of central nervous system functions. The Kv1.2 potassium channels are abundantly expressed in the mammalian brain. The m1 muscarinic acetylcholine receptor is known to increase neuronal excitability by inhibiting a number of potassium channels including the M channel. Despite intense interest and intensive studies for decades, however, how these various potassium channels in central neurons are modulated by acetylcholine remains unknown. The new paradigms established by studies of Peralta's group will provide important guides to future studies.

Ernie will be remembered as much for his open and gentle demeanor as for his substantial scientific achievements. Indeed, his personal and professional style to science was exemplary and he provided a heartening glimpse into what constructive and conscientious scientists can accomplish. He unselfishly shared his ideas with us and he gently critiqued ours. His help was without obligation. He created a laboratory environment that was both nurturing and supportive, and yet remained competitive and exciting. It was a wonderful place for a scientist to learn and grow. In his shortened career, Ernie mentored and trained many scientists. He remained active and intimately involved with their careers until his untimely death.

Ernie touched many of our lives. He was at once generous, inquisitive, insightful and helpful. Although these combined qualities are rare, Ernie showed us that they are not in conflict with success and fulfillment in the too frequently competitive and aggressive world of biomedical research. Ernie's warmth and bright presence in our community will be deeply missed by all of us, but his scientific and personnel legacy will remain as a wonderful source of strength and inspiration.

Lily Jan
David Julius
James Lechleiter

The cover of Science shows gene regulation in developing embryos from the work of Anne Villeneuve (1996 Scholar). Nature illustrates research from the lab of Judith Kimble, on organ development. It is not at all rare for journal covers to feature work of Searle Scholars and Board members, but in the two most widely distributed science journals in the same week is reason for a news blurb!

Matt, who is a Professor in the Department of Developmental Biology at Stanford University School of Medicine, was a pioneer in the molecular basis of pattern formation, working on regulation of the genes involved in setting up overall body plan.

The Sloan Foundation news release names Kevan M. Shokat (1997 Searle Scholar), Jason B. Shear (1998 Searle Scholar), Frederic E. Theunissen and Phyllis I. Hanson (both 1999 Searle Scholars) among its new awardees. The Sloan Foundation Fellowships support outstanding young scientists in the fields of physics, chemistry, computer science, mathematics, neuroscience and economics. The awards are of $35,000 for a two-year period.

CHICAGO, ILLINOIS - Fifteen individuals doing research in the chemical and biological sciences will each have an additional $180,000 to support their research programs during the next three years. The fifteen have been named as the 1999 Searle Scholars. With the names announced today, 318 Searle Scholars have shared over $55,080,000 in grants made since the program began in 1981. This year, 167 applications were considered from recently appointed assistant professors, nominated by 94 universities and research institutions. The final selection of Scholars was based on recommendations made by a committee of eleven scientists distinguished for their research and leadership in the scientific fields of interest to the Searle Scholars Program.

In selecting the Scholars, the committee looked for individuals who have already demonstrated innovative research and who have given evidence of having the potential to make significant contributions to biological research over an extended period of time.

The funds that support the awards come from trusts established under the wills of John G. and Frances C. Searle. Mr. Searle was President of G.D. Searle & Co., of Skokie, Illinois, a research-based pharmaceutical company. Mr. and Mrs. Searle expressed the wish that some of the proceeds of their estates be used for the support of research in medicine, chemistry, and biological science.

In 1980, members of the Searle family acting as Consultants to the Trustees of the Trusts established under the wills of Mr. & Mrs. John G. Searle, recommended the development of a program of support for young biomedical scientists. This idea evolved into the Searle Scholars Program, which is funded through grants from the family trusts to The Chicago Community Trust and administered by Kinship Foundation in Northbrook, Illinois.

1999 Searle Scholars Class

Carrolee Barlow
Salk Institute
Molecular analysis of the neurologic phenotype in Atm deficient mice, a model of the human disease Ataxia Telangiectasia

Brendan P. Cormack
Johns Hopkins University
A genetic analysis of virulence in the asexual Diploid Candida albicans

Kevin H. Gardner
University of Texas Southwestern Medical Center
Structural studies of PAS domains and their complexes involved in eukaryotic transcriptional regulation

Rachel D. Green
Johns Hopkins University
Defining and evolving the peptidyl transferase center of the ribosome

Phyllis I. Hanson
Washington University
Assembly and disassembly of protein complexes in the nerve terminal

Pehr A.B. Harbury
Stanford University
Full structure / full sequence protein design: Computationally engineering alpha/beta barrels

Jin Jiang
University of Texas Southwestern Medical Center
Genetic and biochemical characterization of novel components in the wingless/Wnt signaling pathway

Ka Yee C. Lee
University of Chicago
Lipid-protein interactions in lung surfactant system

Karolin Luger.
Colorado State University
X-ray crystallographic studies on transcription factor binding in a nucleosomal context

William W. Metcalf
University of Illinois
Genetic analysis of methanogenesis by Methanosarcina species

Dale A. Ramsden
University of North Carolina at Chapel Hill
Transposition and V(D)J recombination: A threat to genome stability?

Pamela Schwartzberg
N.I.H.
Functional analysis of Btk/Tec family kinsases in T lymphocytes

Yigong Shi
Princeton University
Structural studies of the Smad protein in TGF-b signaling

Frederic E. Theunissen
University of California, Berkeley
Forebrain auditory processing and vocal learning in songbirds

Ding Xue
University of Colorado
Genetic and biochemical analysis of programmed cell death in the nematode C. elegans

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Linda received this award in recognition of "important discoveries on the nature of the regulation of cell surface receptors that could lead to new therapies for the treatment of cancer and diabetes."

Chi-Huey, a 1985 Searle Scholar and a professor in the Department of Chemistry at the Scripps Research Institute, does research on a wide variety of projects aimed at developing new synthetic methods and strategies, including the development of aminoglycoside antibiotics.

The ASCB Annual Meeting will be held this year December 11-16 in Washington, D.C.