PHYSIOLOGY & BIOPHYSICS RESRACH RETREAT

The Biophysical Society has selected Professor Stephen H. White as the recipient of the 2009 Avanti Award in Lipids for his novel findings in the areas of membrane structure and protein insertion into membranes. The honor will be presented to Dr. White at the 2009 Annual Meeting in Boston.

We welcome our newest faculty member, Dr. Albert Zlotnik, to the Department of Physiology & Biophysics. Dr. Zlotnik is appointed as a member of our Department and in conjunction with the PRIME-LC program. Dr. Zlotnik is an internationally recognized immunologist/molecular biologist with over twenty years experience in both academic science and biotechnology. He has extensive experience in chemokine biology and cancer, and is a highly innovative scientist experienced in the molecular characterization of human diseases using genomic-microarray technologies. Dr. Zlotnik has published more than 170 research papers and holds numerous patents. His research output has been prolific, novel and highly cited: Dr. Zlotnik is recognized by Thompson Scientific ISI as a “Highly Cited Researcher”. (http://isihighlycited.com). This means that a researcher is “among the 250 most cited researchers for their published articles within a specific time-period”. Seven of his citations have been referenced more than 700 times, a remarkable achievement attesting to recognition and productivity on different research topics.

Excellence in Teaching Awards
Physiology & Biophysics Department members were given teaching awards for 2007-2008:

Excellence in Teaching: Dr. Kenneth Longmuir, Dr. K. George Chandy, and Dr. Harry Haigler

Vincent P. Carroll award for distinguished research: Sindy Wei - Congratulations to Sindy and everyone in the Cahalan lab!

Jay Gargus gave a talk at the Neurobiology of Autism Colloquium, as summarized in the "Autism Speaks" website

http://www.autismspeaks.org/science/scientificmeetings/neurochemistry_colloquium_report.php
Jay Gargus, M.D., Ph.D., began the special session by speaking about mitochondrial dysfunction, opening his talk with a commentary on the Federal Government's recent settlement of one autism case with mitochondrial dysfunction, and MMR vaccine, and the timely nature of the meeting. Recent studies have shown that a subset of autistic subjects is associated with mitochondrial energy deficiency that is identified as impairment in fat and carbohydrate metabolism. This type of mitochondrial defiency is similar, but more subtle than those seen in classic mitochondrial defects. Mild mitochondrial dysfunction has also been found in the subset of autistic patients with a genetic defect on chromosome 15. Dr. Gargus also discussed rare cases of familial autism associated with sudden infant death syndrome (SIDS) or associated with abnormalities in cellular calcium homeostasis.

The Faculty of Science at Stockholm University has resolved to confer the Doctorate of Philosophy honoris causa upon Professor Stephen H. White. The conferment will take place in a ceremony at Stockholm City Hall in September 2008.

Irwin A. Rose Lectureship
The Department held the 2007 Irwin A. Rose Lectureship on December 10, 2007. The event featured a scientific presentation by Dr. Tony Hunter, Ph.D. who spoke on “Cell Signaling, and the Interplay between Phosphorylation and Ubiquitination”. Over 125 guests attended the talk and reception in Dr. Rose’s honor.

2007 Physiology and Biophysics Retreat
The Department held its research retreat at the UCLA Conference Center at Lake Arrowhead in October. The event features scientific presentations by faculty members and a poster session in which graduate students and postdoctoral fellows report their latest findings. The "Outstanding Poster Award" this year was shared by Kym Garrod (Cahalan Lab), Aubin Penna (Cahalan Lab), and Alex Froger (Hall Lab).

More Kudos To Kym
Kym Garrod received the Achievement Rewards for College Scientists (ARCS) Fellowship Award of $20,000 for her work in the Cahalan lab. Kym also won the best poster award ($250) in the Immunology Fair and was selected for support through the NIH Immunology Training Grant. Kym's "lucky poster" also helped her at the |Department Retreat at Lake Arrowhead, where she was selected along with Aubin Penna and Alex Froger for poster awards.

After he graduated from George Chandy's lab, Aaron Kolski-Andreaco became the Scientific Editor for the Journal of Visualized Experiments (JoVE; www.jove.com). JoVE is published monthly online and is free access for all. It publishes videos of experimental protocols to facilitate sharing of techniques between laboratories. Several members of the Department of Physiology and Biophysics have already shared their protocols on JoVE, and more videos from members of the Department are being filmed and edited for publication in the near future.

- Alexandrine Froger in James Hall's lab has demonstrated how to transform plasmid DNA into E.coli using the heat shock method (http://www.jove.com/Details.htm?ID=253&VID=245).

- Christine Beeton in George Chandy's lab has demonstrated how to induce and monitor active DTH in rats (http://www.jove.com/Details.htm?ID=237&VID=233).

- Christine Beeton and Adriana Garcia in George Chandy's lab have demonstrated how to induce and monitor chronic-relapsing EAE in rats (http://www.jove.com/Details.htm?ID=224&VID=214).

- Shenyuan Zhang in Michael Cahalan's lab has demonstrated how to purify plasmid DNA from bacterial colonies using the Qiagen miniprep kit (http://www.jove.com/Details.htm?ID=247&VID=239).

Excellence in Teaching Awards
Drs. George Chandy and Ken Longmuir received "Excellence in Teaching" awards from the medical students for their contributions to the 2006-2007 Medical Physiology course. In addition, Dr. Longmuir received the "Silver Beaker", the award presented to the most outstanding Basic Science faculty member for the 2006-2007 school year.

William D. Redfield Memorial Fellowship
Kym Garrod was recently awarded the William D. Redfield Memorial Fellowship with a $1000 prize to support her research effort in the Cahalan lab. This fellowship recognizes excellence in research accomplishment by a graduate student within a broadly defined area of molecular biology. Kym was selected for her research project on imaging the dynamics of natural killer cells and their role in tissue rejection, one part of which has recently been accepted for publication by the Proceedings of the National Academy of Sciences. Kym not only is excelling in her thesis research, but she has also been a catalyst for scientific interactions in the Department by initiating the Research in Progress seminar series among graduate students and postdocs, and for organizing the ever-popular monthly barbecues. We congratulate Kym and look for her to go on to a highly successful academic career.

Science Magazine’s Signaling Breakthrough of the Year (2005 and 2006)
For the past two years, discoveries from the Cahalan lab have been recognized by Science magazine as Signaling Breakthroughs. T lymphocytes require a rise in intracellular Ca2+ levels to become activated. It has long been known that Ca2+ enters the cell through a particular type of channel, called CRAC for Ca2+ Release-Activated Ca2+ channel. But the molecular identity of the channel and the mechanism of activation remained mysterious until recently. Using RNA interference screening in collaboration with researchers at TorreyPines Therapeutics in LaJolla, Cahalan’s group discovered two key membrane proteins, Stim and Orai, that provide the missing link in the signal transduction cascade from T cell receptor engagement to cell proliferation critical for the immune response. Stim, the Signaling Breakthrough for 2005, is a dual purpose molecule. It senses the Ca2+ content within the lumen of the endoplasmic reticulum, using an EF-hand motif near the N-terminus, and translocates to the plasma membrane when the Ca2+ store is depleted. Orai, the Signaling Breakthrough for 2006, forms the Ca2+ channel itself following interaction with Stim. The molecular requirements and activation mechanisms of the CRAC channel have been a sort of holy grail in the field of Ca2+ signaling. The Cahalan group has published two Nature papers, a PNAS paper, and a Journal of Cell Biology paper within the past two years describing these discoveries. For more information see the links to Science Magazine:

Natural compounds block autoimmune response in diabetes, arthritis
UCI study identifies how treatment can limit impact of T-cells in autoimmune diseases
Irvine, Calif., November 6, 2006
Natural compounds derived from a sea anemone extract and a shrub plant have been found to block the autoimmune disease response in type-1 diabetes and rheumatoid arthritis, according to University of California, Irvine researchers.
The study shows both in human and animal tests how these compounds work to deter the effect of autoimmune T-cells, white blood cells that attack the body. The goal, according to UCI researchers, is to develop new treatments from these compounds that will target these destructive T-cells while allowing other white blood cells to fight disease and infection.
Study results appear Nov. 6-10 in the Early Online Edition of the Proceedings of the National Academy of Sciences.
The study, led by UC Irvine School of Medicine researchers George Chandy and Christine Beeton, identifies how these compounds work against a type of white blood cells called effector memory T lymphocytes, which play a major role in autoimmunity. Both compounds block an ion channel in these cells that prevents the cells from proliferating and producing chemicals called cytokines that attack the body during autoimmune disease states.
“Autoimmune diseases affect millions of Americans, and any new therapies that can aid them will have great significance,” Chandy said. “What’s promising about this study is that we identified a protein target on the T-cells that promote autoimmune activity and the compounds that can selectively block the target and shut down the destructive cells.”
White blood cells patrol the body to fight against cancer and infections, but if some of these cells turn against the body they are meant to protect, they cause autoimmune diseases. Millions of people worldwide are afflicted with disabling autoimmune disorders. Two examples of this large class of diseases are type-1 diabetes, in which white blood cells attack the pancreas, and rheumatoid arthritis, in which the joints are attacked.
In their study, the UCI researchers used modified compounds derived from the rue plant (PAP-1) and a Cuban sea anemone extract (SL5), both of which block the ion channel in the destructive T-cells.
In one set of tests using blood samples from type-1 diabetes patients and joint fluid from people with rheumatoid arthritis, the researchers found that both compounds suppressed the function of the autoimmune T-cells without affecting other T-cells that fight infections.
In another set of tests using rats, the compound from the rue shrub plant delayed the onset and reduced the incidence of disease in diabetic rats, while the venom compound stopped the progression of the disease and improved the joint function of rats with experimental autoimmune arthritis. In these rat tests, the compounds were nontoxic.
The Chandy laboratory previously discovered that SL5 compound was effective in treating rats with an experimental model of multiple sclerosis, another devastating autoimmune disease. Preclinical safety studies on PAP-1 and SL5 are under way in collaboration with AIRMID, a biotech company in the San Francisco Bay Area.
“We began our work on these natural products many years ago when we came across a report that described the beneficial effect of a scorpion sting on a patient with multiple sclerosis,” Beeton said. “This work also speaks to the importance of protecting our plant and animal biodiversity – you never know where a new medicine will come from.”
Heike Wulff from University of California, Davis is a co-lead author, and other authors from UCI, UC Davis, Johns Hopkins University, Bachem Biosciences and the Benaroya Research Institute in Seattle are noted in the study text. The National Institutes of Health, American Diabetes Association, Juvenile Diabetes Research Foundation, National Multiple Sclerosis Society, Arthritis National Research Foundation and David Israelsky provided support for this study.
About type-1 diabetes and rheumatoid arthritis: The American Diabetes Association estimates that type-1 diabetes mellitus, also known as juvenile diabetes, affects one in every 400 or 600 children and adolescents in the U.S. It is characterized by a destruction of the cells that produce insulin in the pancreas. Without enough insulin, the body cannot correctly regulate levels of blood glucose, a major source of energy for the body. Type-1 diabetes can lead to serious complications such as heart disease, blindness, and nerve or kidney damage.
In rheumatoid arthritis, white blood cells induce inflammation in the joints, leading to muscle and joint aches, stiffness, and fatigue. According to the Arthritis Foundation, rheumatoid arthritis is one of the most serious and disabling types, affecting mostly women. An estimated 2.1 million people in the U.S. have rheumatoid arthritis. Some recent studies have suggested that the overall number of new cases of rheumatoid arthritis actually may be going down.

Teaching Award
Professor K. George Chandy was the recipient of the Excellence in Teaching Award for Physiology for 2005/2006.

Space Cycle is Out of this World!
Professor Kenneth M. Baldwin of Physiology and Biophysics and Professor Vincent Caiozzo of Orthopedic Surgery are developing the Space Cycle to prevent muscle atrophy on long missions to Mars. To power the Space Cycle, two astronauts ride opposite each other around a pole, one pedaling the bike-like device and the other performing squat exercises on a platform. As they spin, they create artificial gravity, resulting in a kind of full-body resistance training. Scientists hope the gravitational weight will help boost muscle mass, bone density and cardiovascular fitness.

Honor Award
Professor Kenneth M. Baldwin was presented with the Honor Award by the Environmental and Exercise Physiology Section of the American Physiological Society (APS). The award is the highest level of recognition for excellence in research that is given within the various Science Sections that comprise the APS. Congratulations!

Ralph Alden Bradshaw 65th Birthday Symposium"From Proteins to Proteomics"
The symposium will feature fifteen speakers who are either former students or close friends and collaborators of Dr. Bradshaw's. It has been organized into four sessions including talks on protein structure, cell biology, cell signaling, and the fibroblast growth factor family of proteins. Sir Tom Blundell will give the opening lecture the night before.

Nancy Allbritton, Cell Detective!
Professor Nancy Allbritton was featured “In the lab” on Friday, March 17, 2006 in the OC Register. Dr. Allbritton’s work stretches from physiology to chemistry to biophysics and biomedical engineering. Most of it is in the service of understanding cells. The focus of Dr. Allbritton’s research looks at the molecular circuitry of cells in living humans and animals. Working with others, she designed better “micropallet arrays” for scientists who want to investigate cells faster and more effectively. She also made it easier to gather cells that warrant a closer look by geneticists and biochemists. According to Dr. Allbritton, “Our understanding of how our bodies work is rapidly evolving because we are learning how cells work at the molecular level. My research brings together principles from chemistry, physics and engineering to study the dynamic interplay of molecules with each cell."

Biophysical Society's 2006 New and Notable Symposium
Professor Jim Hall was selected to give a talk in the Biophysical Society's 2006 New and Notable Symposium at the annual meeting in Salt Lake City. Hall s talk, Amyloid oligomers increase membrane conductance by altering dielectric structure , will be one of four which were selected for the symposium out of more than 150 nominated by society members and others. Although the title does not mention Alzheimer s Disease, the talk will present a new mechanism for the toxic effects of amyloids which are thought to be the root cause of Alzheimer s. The work is a collaboration between three labs at UCI, Hall's, Charles Glabe's and Mike Cahalan's and a group at NIST, the National Institute of Standards and Technology in Gaithersburg Maryland.

WHAT A HEADACHE!!!
Professor J. Jay Gargus has been selected to receive the "National Headache Foundation Lectureship Award" for 2006 for his work on genetic causes of migraine. Dr. Gargus discovered how specific mutations of the sodium/potassium pump (ATP1A2) causes a rare dominantly inherited migraine syndrome in families. Migraine has a strong genetic component, but is most commonly a complex polygenic trait. Recently, however, reports of rare inherited Mendelian dominant migraine with aura, Familial Hemiplegic Migraine (FHM), have provided important insight into migraine pathophysiology. Mutations in voltage-gated calcium and sodium channels can also cause FHM, and now Dr. Gargus' work has shown how the sodium pump, an enzyme transporter that sets concentration gradients for sodium and potassium across plasma membranes, can also result in the phenotype of migraine headache (see Segall et al J Biol Chem 279:43692-43696, 2004; Segall et al Proc. Nat. Acad. Sci. USA 102:11106-11111, 2005). This award is generously underwritten by an unrestricted educational grant from Merck & Co., Inc. Dr. Gargus' lecture titled “Molecular lesions underlying Familial Hemiplegic Migraine provide insights into migraine pathogenesis and potential drug targets” reflects an extended collaboration between the Departments of Physiology & Biophysics and Pediatrics, section of Human Genetics, at the University of California, Irvine, and the Departments of Biochemistry and Medicine, at McGill University, Montreal, Canada and will be presented at the National Headache Foundation’s 3^rd Annual Headache Research Summit in Palm Springs on Thursday, February 16.

Michael D. Cahalan, Ph.D., Recipient of the NINDS Javits Award
The National Institute of Neurological Disorders and Stroke (NINDS), a part of the National Institutes of Health, has named six scientists to receive its prestigious Senator Jacob Javits Award in the Neurosciences. The award is given to individual investigators who have demonstrated exceptional scientific excellence and productivity in research supported by the NINDS and who are expected to conduct innovative research over the next 7 years.

Authorized by the Congress in 1983, the award honors the late U.S. Senator Jacob K. Javits (R-NY), who was a strong advocate for research on a variety of neurological disorders. Senator Javits suffered from amyotrophic lateral sclerosis, the disabling neurodegenerative disease also known as Lou Gehrig’s disease.

The Award guarantees funding for 4 years, after which 3 additional years may be awarded pending receipt and approval of additional information. Investigators are nominated by either NINDS staff or members of the National Advisory Neurological Disorders and Stroke Council, from a pool of competing applicants during a grants cycle. The Council must approve each recommendation, with final selection being made by the NINDS Director.

Michael D. Cahalan, Ph.D., Professor of Physiology and Biophysics, University of California, Irvine.
An immunologist, Dr. Cahalan is deeply interested in how T lymphocytes (white blood cells that help the body fight off infection) function at the molecular and cellular levels. He is also interested in diseases such as multiple sclerosis, which are thought to have an immune component. T lymphocytes possess numerous ion channels, which are intimately involved in the immune response and offer promising targets for development of immune system therapeutic agents. His Javits award will allow him to study the role calcium release-activated calcium channels play in T cell responses, as well as to identify the molecular basis for channel gating and the corresponding cellular response in immune system activity.

Dr. Janos Lanyi was awarded the MERIT Award extension by the National Advisory General medical Sciences Council in 2005 for his project “Light-Driven Ion Transport in Bacterial Rhodopsins”. Dr. Lanyi will receive an additional five years of support without having to submit a competing application.

Dr. Jay Gargus was nominated by the University of Hawaii for a nationally-competitive Federation of American Societies for Experimental Biology (FASEB) Visiting Professor award, which he received, allowing him to lecture and mentor junior faculty at the University of Hawaii.

Dr. Kenneth Baldwin was awarded the NASA Public Service Medal Award for Advisory Committee Service in 2005. This is the second NASA service medal that Dr. Baldwin has received. The first was awarded in 1999 for his accomplishments in space research.

2005 Physiology and Biophysics Retreat
The Department held its research retreat at the UCLA Conference Center at Lake Arrowhead on October 2, 3, and 4. The event features scientific presentations by faculty members and a poster session in which graduate students and postdoctoral fellows report their latest findings. The "Outstanding Poster Award" this year was shared by Christine Beeton (Chandy Lab), Melanie Matheu (Cahalan Lab), Sindy Wei (Cahalan Lab), and Shenyuan Zhang (Cahalan Lab).

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