Department News

Molecular economics: New computer models calculate systems-wide costs of gene expression

August 7, 2012

Bioengineers at the University of California, San Diego have developed a method of modeling, simultaneously, an organism’s metabolism and its underlying gene expression.  In the emerging field of systems biology, scientists model cellular behavior in order to understand how processes such as metabolism and gene expression relate to one another and bring about certain characteristics in the larger organism.

In addition to serving as a platform for investigating fundamental biological questions, this technology enables far more detailed calculations of the total cost of synthesizing many different chemicals, including biofuels.  Their method accounts, in molecular detail, for the material and energy required to keep a cell growing, the research team reported in the journal Nature Communications.

“With this new method, it is now possible to perform computer simulations of systems-level molecular biology to formulate questions about fundamental life processes, the cellular impacts of genetic manipulation or to quantitatively analyze gene expression data,” said Joshua Lerman, a Ph.D. candidate in Bernhard Palsson’s Systems Biology Research Group.

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Tumor Cells' Inner Workings Predict Cancer Progression

July 27, 2012

Using a new assay method to study tumor cells, researchers at the University of California, San Diego School of Medicine and UC San Diego Moores Cancer Center have found evidence of clonal evolution in chronic lymphocytic leukemia (CLL). The assay method distinguishes features of leukemia cells that indicate whether the disease will be aggressive or slow-moving, a key factor in when and how patients are treated.

The findings are published in the July 26, 2012 First Edition online issue of Blood.

Coauthors include two members of the Bioinformatics program: alumnus Han-Yu Chuang, Ph.D. (lead author) and Prof. Trey Ideker.

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Discovery of Chemical That Affects Biological Clock Offers New Way to Treat Diabetes

July 12, 2012

Biologists at UC San Diego have discovered a chemical that offers a completely new and promising direction for the development of drugs to treat metabolic disorders such as type 2 diabetes—a major public health concern in the United States due to the current obesity epidemic.

Their discovery, detailed in a paper published July 13 in an advance online issue of the journal Science, initially came as a surprise because the chemical they isolated does not directly control glucose production in the liver, but instead affects the activity of a key protein that regulates the internal mechanisms of our daily night and day activities, which scientists call our circadian rhythm or biological clock.

The team was headed by Prof. Steve Kay, dean of the Division of Biological Sciences and a faculty member of the Bioinformatics and Systems Biology program.

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Gene Mutations Cause Massive Brain Asymmetry

June 25, 2012

Hemimegalencephaly is a rare but dramatic condition in which the brain grows asymmetrically, with one hemisphere becoming massively enlarged. Though frequently diagnosed in children with severe epilepsy, the cause of hemimegalencephaly is unknown and current treatment is radical: surgical removal of some or all of the diseased half of the brain.

In a paper published in the June 24, 2012 online issue of Nature Genetics, a team of doctors and scientists, led by researchers at the University of California, San Diego School of Medicine and the Howard Hughes Medical Institute, say de novo somatic mutations in a trio of genes that help regulate cell size and proliferation are likely culprits for causing hemimegalencephaly, though perhaps not the only ones.

Coauthors include two Bioinformatics and Systems Biology program members: Joseph G. Gleeson, M.D., and Vineet Bafna, Ph.D.

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Varying Drug Levels in the Body Could Speed the Emergence of Drug-Resistant Bacteria

June 19, 2012

Strains of bacteria able to resist multiple antibiotics pose a growing threat to public health, yet the means by which resistance quickly emerges aren’t well understood. Scientists led by physics professor Terence Hwa at the University of California, San Diego, thought that the variety of environments in which bacteria encounter antibiotic drugs could play an important role. They have developed a mathematical model, published in the June 18 early online edition of the Proceedings of the National Academy of Sciences, that demonstrates how that would work.

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Sequencing Protein-making Part of Genome Can Change Diagnosis and Patient Care

June 13, 2012

In the June 13 issue of Science Translational Medicine, an international team led by researchers from the University of California, San Diego School of Medicine reports that the new technology of exome sequencing is not only a promising method for identifying disease-causing genes, but may also improve diagnoses and guide individual patient care.

In exome sequencing, researchers selectively and simultaneously target and map all of the portions of the genome where exons reside. Exons are short, critical sequences of DNA in genes that are translated into proteins – the biological workhorses involved in virtually every cellular function, plus various structural or mechanical duties.

The researchers, headed by principal investigator Joseph G. Gleeson, MD, professor of neurosciences and pediatrics at UC San Diego and Rady Children’s Hospital-San Diego, sequenced the exomes of 118 patients who had been diagnosed with specific neurodevelopmental diseases. In each of the cases, all known genetic causes of their disease had been previously excluded.

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UC San Diego Researchers Receive New CIRM Funding

May 25, 2012

Five scientists from the University of California, San Diego and its School of Medicine have been awarded almost $12 million in new grants from the California Institute for Regenerative Medicine (CIRM) to conduct stem cell-based research into regenerating spinal cord injuries, repairing gene mutations that cause amyotrophic lateral sclerosis and finding new drugs to treat heart failure and Alzheimer’s disease.  Awardees include two faculty members in the Bioinformatics and Systems Biology Program: Lawrence Goldstein, who is studying Alzheimer's Disease, and Gene Yeo, who is studying Lou Gehrig's disease.

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New Drug Target Improves Memory in Mouse Model of Alzheimer’s Disease

May 7, 2012

Researchers at the University of California, San Diego, the Medical University of South Carolina, the University of Cincinnati, and American Life Science Pharmaceuticals of San Diego have validated the protease cathepsin B (CatB) as a target for improving memory deficits and reducing the pathology of Alzheimer’s disease (AD) in an animal model representative of most AD patients.  The study has been published in the online edition of the Journal of Alzheimer’s Disease.

According to investigator Vivian Y. H. Hook, PhD, professor of the UCSD Skaggs School of Pharmacy and Pharmaceutical Sciences and professor of neurosciences, pharmacology and medicine at the UCSD School of Medicine, and professor in the Bioinformatics and Systems Biology Graduate Program, the study is important because it could lead to new therapeutics that improve the memory deficits of AD.

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Ruth Williams Elected to National Academy of Sciences

May 1, 2012

The National Academy of Sciences today elected three professors at the University of California, San Diego to membership in the prestigious National Academy of Sciences, one of the highest honors bestowed on U.S. scientists and engineers. Roberto Malinow, Ruth Williams and William Young were among the 84 new members and 21 foreign associates elected to the academy today “in recognition of their distinguished and continuing achievements in original research.” Ruth Williams, a professor in the Department of Mathematics, is a member of the Graduate Program in Bioinformatics and Systems Biology.

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Express Yourself: How Zygotes Sort Out

February 16, 2012

Writing in the February 17, 2012 issue of the journal Cell, researchers at the Ludwig Institute for Cancer Research, the University of California, San Diego School of Medicine and the Toronto Western Research Institute peel away some of the enduring mystery of how zygotes or fertilized eggs determine which copies of parental genes will be used or ignored.

In the Cell paper, a team of scientists, led by Bing Ren, PhD, head of the Laboratory of Gene Regulation at the Ludwig Institute for Cancer Research at UC San Diego, describe in greater detail how differential DNA methylation in the two parental genomes set the stage for selective expression of imprinted genes in the mouse. Differential DNA methylation is essential to normal development in humans and other higher organisms. It involves the addition of hydrocarbon compounds called methyls to cytosine, one of the four bases or building blocks of DNA. Such addition alters the expression of different genes, boosting or suppressing them to help direct embryonic growth and development.

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