Welcome to the biweekly electronic newsletter from Stanford Bio-X for members of the Bio-X Corporate Forum. Please contact Dr. Hanwei Li, the Bio-X Corporate Forum Liaison if you would like to be added or removed from this distribution list, or if you have any questions about Stanford Bio-X or Stanford University.

Highlights

** On October 9, 2013, Bio-X celebrated the 10th Anniversary of the James H. Clark Center, the hub of Bio-X. Check out CLARK CENTER @ 10X as well as the Bio-X Timeline over the last 15 years!!

** Check out the article by Stanford President John Hennessy in the Nov/Dec 2013 issue of the Stanford Magazine on Bio-X and the Clark Center, "A Cauldron of Innovation".

Bio-X Core Programs

SEED GRANTS FOR SUCCESS - Stanford Bio-X Interdisciplinary Initiatives Program (IIP) The Bio-X Interdisciplinary Initiatives Program represents a key Stanford Initiative to address challenges in human health. The IIP awards approximately $3 million every other year in the form of two-year grants averaging about $150,000 each. From its inception in 2000 through the fifth round in 2010, the program has provided critical early-stage funding to 114 different interdisciplinary projects, involving collaborations from over 300 faculty members, and creating over 450 teams from five different Stanford schools. From just the first 5 rounds, the IIP awards have resulted in a 10-fold-plus return on investment, as well as hundreds of publications, dozens of patents filed, and most importantly, the acceleration of scientific discovery and innovation. 2014 is the start of the 7th round of the Bio-X IIP Seed Grants Program, and 22 newly awarded projects were selected from 142 Letters of Intent (LOIs)! This has been the largest number of LOIs that Bio-X has received. Please go here to check out the newly awarded projects. Competition was intense, and the selection criteria included innovation, high-reward, and new interdisciplinary collaborations. (To view the 142 other IIP projects that have been funded from the previous 6 rounds, please click here.)

Bio-X FELLOWSHIPS Every year, graduate students and postdoctoral scholars of Bio-X affiliated faculty are highly encouraged to apply for the Bio-X Fellowships, which are awarded to research projects that are interdisciplinary and utilize the technologies of different fields to solve different biological questions. Students are encouraged to work collaboratively with professors of different departments, thus creating cross-disciplinary relationships among the different Stanford schools. Our fellows have conducted exciting research, resulting in publications in high-impact journals and have been offered excellent positions in industry and academia. To date, with the 19 new awardees of 2014, Stanford Bio-X has a total of 173 Fellows. You can view the numerous Fellowship projects that have been awarded over the years as well as oral presentations from previous symposiums here.

Bio-X UNDERGRADUATE SUMMER RESEARCH PROGRAM The Bio-X Undergraduate Summer Research Program supports undergraduate research training through an award designed to support interdisciplinary undergraduate summer research projects. The program is an invaluable opportunity for students to conduct hands-on research, learn how to carry out experiments in the laboratory, and develop the skills to read and analyze scientific literature. This program is eligible to Stanford students who want to work in the labs of Bio-X affiliated faculty. To date, with 65 new awardees from 154 applications submitted this year, 306 students have been awarded the opportunity to participate in the Bio-X Undergraduate Summer Research Program. Participating undergraduates are also required to present poster presentations on the research that they've conducted during the program. Please click here for title lists of past posters that our undergraduates have presented.

News

Stanford chemists take step toward solving mystery of how enzymes work
Bio-X Affiliated Faculty Steven Boxer
Bio-X Fellow Stephen Fried

Open any biology or chemistry textbook and entire chapters will be dedicated to detailing molecular processes crucial to life that are only made possible by seemingly magical proteins called enzymes. The magic is not fully understood, however, and each book will offer a somewhat different explanation for how enzymes work. Now, Stanford chemists have peered inside a working enzyme and found that local electric fields focused at the active site might play a big role in helping it accelerate reactions. The results are published in the current issue of Science. Without enzymes, life wouldn't be possible. Nearly every process in cells – DNA replication, protein synthesis, metabolism of food into energy and even steroid production – is made possible by an enzyme interacting specifically with its target substrate to transform it into something useful. Oftentimes, the reaction is so slow that it would take billions of years to occur without the enzyme's involvement. Enzymes can accelerate these slow reactions by up to 25 orders of magnitude, and with great selectivity. But when scientists have tried to design new enzymes, even by following the atomic blueprint of well-studied enzymes, things just don't seem to click. "Clearly it's important to have the right pieces in place, but there seems to be something more," said Steven Boxer, the Camille and Henry Dreyfus Professor of Chemistry at Stanford, and senior author on the new study. "There are a lot of really strong opinions about this, but one idea that's emerged, mostly from simulations, is that electrostatic interactions within the enzyme might play an important role lowering the barrier for the reaction, but we haven't had a way to measure this until now."

Stem cells faulty in Duchenne muscular dystrophy, researchers find
Bio-X Affiliated Faculty Thomas Rando

Like human patients, mice with a form of Duchenne muscular dystrophy undergo progressive muscle degeneration and accumulate connective tissue as they age. Now, researchers at the Stanford University School of Medicine have found that the fault may lie at least partly in the stem cells that surround the muscle fibers. They’ve found that during the course of the disease, the stem cells become less able to make new muscle and instead begin to express genes involved in the formation of connective tissue. Excess connective tissue — a condition called fibrosis — can accumulate in many organs, including the lungs, liver and heart, in many different disorders. In the skeletal muscles of people with muscular dystrophy, the fibrotic tissue impairs the function of the muscle fibers and leads to increasing weakness and stiffness, which are hallmarks of the disease. The researchers discovered that this abnormal change in stem cells could be inhibited in laboratory mice by giving the animals a drug that is already approved for use in humans. The drug works by blocking a signaling pathway involved in the development of fibrosis. Although much more research is needed, the scientists are hopeful that a similar approach may one day work in children with muscular dystrophy.

Skin patch could help heal, prevent diabetic ulcers, study finds
Bio-X Affiliated Faculty Geoffrey Gurtner

Researchers at the Stanford University School of Medicine say they have developed a safe and effective skin patch to deliver a drug that enhances the healing of diabetes-related ulcers. The patch, which they tested in mice, may also serve as a way to prevent ulcer formation. Among the more than 29 million people in the United States with either type-1 or type-2 diabetes, an estimated 15 percent develop ulcers. The ulcers, sores or open wounds that usually occur on the foot, become a secondary health condition that leads to prolonged disability, high rates of recurrence and increased mortality. Nonhealing wounds related to diabetes are the leading cause of nontraumatic amputations in the country. What causes these ulcers has been known for several years. In 2009, researchers led by Geoffrey Gurtner, MD, a professor of surgery at Stanford, and a group of scientists at the Albert Einstein College of Medicine published a study pinpointing exactly how diabetes reduces the ability of tissue to form new blood vessels essential for wound healing: High levels of blood sugar compromise the body’s ability to grow the new blood vessels. That same study found a potential treatment: deferoxamine, or DFO, a drug already approved by the Food and Drug Administration to treat hemochromatosis, a condition in which too much iron accumulates in the body. DFO can correct the diabetes-impaired expression of a protein that supports new vascular growth. The problem was how to deliver the DFO, which would be toxic if used for as long as diabetic pressure ulcers can take to heal. So the researchers decided to investigate an alternative: local delivery of just enough medication directly to an ulcer through a patch applied to the skin.

Newly identified molecular network in brain implicated in autism, researchers say
Bio-X Affiliated Faculty Michael Snyder

A defect in communication between the two halves of the brain may be responsible for some cases of autism, according to a study by researchers at the Stanford University School of Medicine. They came to their conclusions by analyzing what's called the human interactome — a vast network of interacting proteins - and by sequencing genomes and analyzing gene expression patterns in individuals with autism. The study offers a possible explanation as to why the communication center of the brain, called the corpus callosum, is often abnormally small in people with the condition. Although most research has focused on neurons, this study also implicates the oligodendrocytes in the disorder. Oligodendrocytes coat the signaling arms of a neuron with an insulating substance called myelin, which enables electrical signals to move quickly from one neuron to another. "This is our first glimpse of autism's underlying biological framework, and it implicates a cell type and region of the brain that have not been extensively studied in this disease," said Michael Snyder, PhD, professor and chair of genetics. "Until now, we've suspected that autism could be the result of defects in the neurons themselves. Now it appears that the oligodendrocytes can contribute to the problem by inhibiting neuronal signaling through poor cellular differentiation and myelination."

Events

Resources

To learn more about Stanford Bio-X or Stanford University, please contact Dr. Hanwei Li, the Bio-X Corporate Forum Liaison, at 650-725-1523 or lhanwei1@stanford.edu, or Dr. Heideh Fattaey, the Executive Director of Bio-X Operations and Programs, at 650-799-1608 or hfattaey@stanford.edu.