May 21, 2013.
First sequenced genomes include salmonella, listeria, other foodborne microorganisms.
Striking a blow at foodborne diseases, the 100K Pathogen Genome Project at the University of California, Davis, today announced that it has sequenced the genomes of its first 10 infectious microorganisms, including strains of Salmonella and Listeria.
“We are creating a free, online encyclopedia or reference database of genomes so that during a foodborne disease outbreak, scientists and public health professionals can quickly identify the responsible microorganism and track its source in the food supply using automated information-handling methods,” said professor Bart Weimer, director of the 100K Genome Project and co-director of BGI@UC Davis, the Sacramento facility where the sequencing is carried out.
Weimer estimates that the availability of this genomic information will cut in half the time necessary to diagnose and treat foodborne illnesses, and will enable scientists to make discoveries that can be used to develop new methods for controlling disease-causing microorganisms in the food chain.
The project is dedicated to sequencing the genomes of 100,000 bacteria and viruses that cause serious foodborne illnesses in people around the world.
May 10, 2013.
Discovery shows positive effects of drugs that may lead to effective new therapies for A-T.
Richard Gatti, UCLA
Led by Dr. Peiyee Lee and Dr. Richard Gatti, researchers at the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA have used induced pluripotent stem (iPS) cells to advance disease-in-a-dish modeling of a rare genetic disorder, ataxia telangiectasia (A-T).
Their discovery shows the positive effects of drugs that may lead to effective new treatments for the neurodegenerative disease. IPS cells are made from patients’ skin cells, rather than from embryos, and they can become any type of cells, including brain cells, in the laboratory. The study appears online ahead of print in the journal Nature Communications.
People with A-T begin life with neurological deficits that become devastating through progressive loss of function in a part of the brain called the cerebellum, which leads to severe difficulty with movement and coordination. A-T patients also suffer frequent infections due to their weakened immune systems and have an increased risk for cancer. The disease is caused by lost function in a gene, ATM, that normally repairs damaged DNA in the cells and preserves normal function.
Developing a human neural cell model to understand A-T’s neurodegenerative process — and create a platform for testing new treatments — was critical because the disease presents differently in humans and laboratory animals. Scientists commonly use mouse models to study A-T, but mice with the disease do not experience the more debilitating effects that humans do. In mice with A-T, the cerebellum appears normal and they do not exhibit the obvious degeneration seen in the human brain.
May 7, 2013.
UCLA research sheds light on growth of head and neck squamous cell carcinomas.
Cun-Yu Wang, UCLA
Very little has been known about the epigenetic events — developmental and environmental factors affecting genes — that occur prior to the invasive growth of head and neck squamous cell carcinomas and their spread to other parts of the body, or metastasis.
However, researchers from the UCLA School of Dentistry discovered what could be a crucial step toward understanding the process that activates the cancer cells. Squamous cell carcinoma is known for being one of the most deadly and debilitating types of tumors.
Led by Dr. Cun-Yu Wang, a UCLA School of Dentistry professor and leading cancer scientist, the group identified the key epigenetic factor KDM4A, which modifies the molecular activation process of protein AP-1. AP-1 is known to regulate gene expression and promote metastasis of squamous cell carcinoma. Their findings show that squamous cell carcinoma’s invasive growth could potentially be repressed by targeting KDM4A.
May 7, 2013.
UCLA biologists identify gene that could extend healthy life span in humans.
David Walker, UCLA
UCLA life scientists have identified a gene previously implicated in Parkinson’s disease that can delay the onset of aging and extend the healthy life span of fruit flies. The research, they say, could have important implications for aging and disease in humans.
The gene, called parkin, serves at least two vital functions: It marks damaged proteins so that cells can discard them before they become toxic, and it is believed to play a key role in the removal of damaged mitochondria from cells.
“Aging is a major risk factor for the development and progression of many neurodegenerative diseases,” said David Walker, an associate professor of integrative biology and physiology at UCLA and senior author of the research. “We think that our findings shed light on the molecular mechanisms that connect these processes.”
In the research, published today in the early online edition of the journal Proceedings of the National Academy of Sciences, Walker and his colleagues show that parkin can modulate the aging process in fruit flies, which typically live less than two months. The researchers increased parkin levels in the cells of the flies and found that this extended their life span by more than 25 percent, compared with a control group that did not receive additional parkin.
“In the control group, the flies are all dead by Day 50,” Walker said. “In the group with parkin overexpressed, almost half of the population is still alive after 50 days. We have manipulated only one of their roughly 15,000 genes, and yet the consequences for the organism are profound.”
May 3, 2013.
UCSF scientist says new approach could “democratize” viral surveillance.
Lone Star tick, Amblyomma americium
The tick-borne Lone Star virus has been conclusively identified as part of a family of other tick-borne viruses called bunyaviruses, which often cause fever, respiratory problems and bleeding, according to new research led by scientists at UC San Francisco.
What made the work especially promising, said principal investigator Charles Chiu, M.D., Ph.D., was the speed at which the virus was definitively identified. The team used a new approach to gene sequencing that enabled them to completely reconstruct the virus’ previously unknown genome in less than 24 hours – significantly faster than conventional sequencing techniques, which can take days to weeks.
The technique, called ultra-rapid deep sequencing, combines deep sequencing – an emerging technology that reconstructs an entire DNA sequence from a tiny snippet of DNA – with advanced computational techniques and algorithms developed in the laboratories of Chiu and his research collaborators.
Chiu, an assistant professor of laboratory medicine at UCSF and director of the UCSF-Abbott Viral Diagnostics and Discovery Center, reported the results in a paper published in PloS ONE on April 29.
May 1, 2013.
Research by UCSF-led team opens door to potential new treatments for pounding headaches.
Louis Ptacek, UC San Francisco
A UC San Francisco-led research team has identified a genetic mutation that is strongly associated with a typical form of migraine.
In a paper published today (May 1) in Science Translational Medicine, the team linked the mutation with evidence of migraine in humans, in a mouse model of migraine and in cell culture in the laboratory.
The mutation is in the gene known as casein kinase I delta (CKIdelta).
“This is the first gene in which mutations have been shown to cause a very typical form of migraine,” said senior investigator Louis J. Ptácek, a Howard Hughes Medical Institute investigator and a professor of neurology at UCSF. “It’s our initial glimpse into a black box that we don’t yet understand.”
April 25, 2013.
With two new methods, UC San Diego scientists hope to improve genome-wide association.
As scientists probe and parse the genetic bases of what makes a human a human (or one human different from another), and vigorously push for greater use of whole genome sequencing, they find themselves increasingly threatened by the unthinkable: Too much data to make full sense of.
In a pair of papers published in today’s (April 25) issue of PLOS Genetics, two diverse teams of scientists, both headed by researchers at the UC San Diego School of Medicine, describe novel statistical models that more broadly and deeply identify associations between bits of sequenced DNA called single nucleotide polymorphisms or SNPs and say lead to a more complete and accurate understanding of the genetic underpinnings of many diseases and how best to treat them.
“It’s increasingly evident that highly heritable diseases and traits are influenced by a large number of genetic variants in different parts of the genome, each with small effects,” said Anders M. Dale, Ph.D., a professor in the departments of radiology, neurosciences and psychiatry at the UC San Diego School of Medicine. “Unfortunately, it’s also increasingly evident that existing statistical methods, like genome-wide association studies (GWAS) that look for associations between SNPs and diseases, are severely underpowered and can’t adequately incorporate all of this new, exciting and exceedingly rich data.”
April 25, 2013.
Discover could help in development of drugs to fight diseases.
Shengben Li (left) is a postdoctoral researcher in the lab of Xuemei Chen at UC Riverside.
RNA molecules, made from DNA, are best known for their role in protein production. MicroRNAs (miRNAs), however, are short (~22) nucleotide RNA sequences found in plants and animals that do not encode proteins but act in gene regulation and, in the process, impact almost all biological processes — from development to physiology to stress response.
Present in almost in every cell, microRNAs are known to target tens to hundreds of genes each and to be able to repress, or “silence,” their expression. What is less well understood is how exactly miRNAs repress target gene expression.
Now a team of scientists led by geneticists at the University of California, Riverside has conducted a study on plants (Arabidopsis) that shows that the site of action of the repression of target gene expression occurs on the endoplasmic reticulum (ER), a cellular organelle that is an interconnected network of membranes — essentially, flattened sacs and branching tubules — that extends like a flat balloon throughout the cytoplasm in plant and animal cells.
“Our study is the first to demonstrate that the ER is where miRNA-mediated translation repression occurs,” said lead researcher Xuemei Chen, a professor of plant cell and molecular biology and a Howard Hughes Medical Institute-Gordon and Betty Moore Foundation investigator. “To understand how microRNAs repress target gene expression, we first need to know where microRNAs act in the cell. Until now no one knew that membranes are essential for microRNA activity. Our work shows that an integral membrane protein, AMP1, is required for the miRNA-mediated target gene repression to be successful. As AMP1 has counterparts in animals, our findings in plants could have broader implications.”
Study results appear today in the journal Cell.
April 24, 2013.
Finding in fruit flies could help humans.
Puncturing a Drosophila embryo with the enzyme trypsin activates genes throughout the epidermis that help in wound healing, shown in green.
Biologists at UC San Diego have identified eight genes never before suspected to play a role in wound healing that are called into action near the areas where wounds occur.
Their discovery, detailed this week in the open-access journal PLOS ONE, was made in the laboratory fruit fly Drosophila. But the biologists say many of the same genes that regulate biological processes in the hard exoskeleton, or cuticle, of Drosophila also control processes in human skin. That makes them attractive candidates for new kinds of wound-healing drugs or other compounds that could be used to treat skin ailments.
“Many of the key molecules and proteins involved in Drosophila wound healing are involved in mammalian wound healing,” says Rachel Patterson, the first author who published the paper with Michelle Juarez and William McGinnis, a professor of biology and interim dean of the Division of Biological Sciences. “The genetics of Drosophila are not as complicated as mammalian genetics, so it’s easier to attribute specific biological functions to individual genes.”
April 16, 2013.
Painful, chronic condition often occurs after breast cancer surgery.
Bradley Aouizerat, UC San Francisco
A new UC San Francisco study has found a clear association between certain genes and the development of lymphedema, a painful and chronic condition that often occurs after breast cancer surgery and some other cancer treatments.
The researchers also learned that the risks of developing lymphedema increased significantly for women who had more advanced breast cancer at the time of diagnosis, more lymph nodes removed or a significantly higher body mass index.
The study is the first to evaluate genetic predictors of lymphedema in a large group of women using a type of technology, bioimpedance spectroscopy, to measure increases in fluid in the arm. Bioimpedance spectroscopy is a noninvasive procedure that allows one to measure body composition including an increase in fluid in an arm or a leg.
The study, which involved some 400 women who were tracked over four to five years, will be published online today (April 16) in PLOS ONE.
“The genetic markers found in our study make perfect sense,” said senior author Bradley Aouizerat, Ph.D., a professor at the UCSF School of Nursing in the department of physiological nursing. “These genes are ‘turned on’ later in the development of our lymph system and blood vessels. They appear to play a role in the ability of our lymphatic system to function on an ongoing basis. It is possible in some individuals who have changes in these genes, that lymphedema could develop after an injury like breast cancer surgery because these genes do not function properly.”
April 15, 2013.
UCSF study makes significant progress toward mouse model of human autism.
Elliott Sherr, UC San Francisco
For the first time, researchers have linked autism in a mouse model of the disease with abnormalities in specific regions of the animals’ chromosomes.
The regions contain genes associated with aberrant brain development and activity.
“These discoveries in mice may eventually pave the way towards understanding autism in human patients and devising new treatments,” said co-senior author, Elliott H. Sherr, M.D., Ph.D., a pediatric neurologist at UCSF Benioff Children’s Hospital and professor of neurology at UC San Francisco.
The findings are reported in a study published today (April 15) in PLOS One.
April 8, 2013.
NIH grant helps UCLA scientist study disorder in African Americans.
Daniel Geschwind, UCLA
The National Institutes of Health has awarded Dr. Daniel Geschwind, director of the UCLA Center for Autism Research and Treatment, a five-year, $10 million grant to continue his research on the genetic causes of autism spectrum disorders and to expand his investigations to include the genetics of autism in African Americans.
The new network grant, which will fund collaborative work by Geschwind and experts at other autism centers around the country, is part of the NIH’s Autism Centers of Excellence program, which was launched in 2007 to support coordinated research into the causes of autism spectrum disorders (ASD) and the discovery of new treatments.
Autism spectrum disorders are complex developmental disorders that affect how a person behaves, interacts with others, communicates and learns. According to the Centers for Disease Control, ASD affects approximately 1 in 88 children in the U.S.
Geschwind’s award will allow him to build on his earlier work identifying genetic variants associated with an increased susceptibility to autism while adding an important new emphasis. The research network he leads — which also includes scientists from the Albert Einstein College of Medicine, Emory University, Johns Hopkins University, Washington University and Yale University — aims to recruit at least 600 African American families who have a child diagnosed with an ASD for genetic testing.