Genetic Engineering & Biotechnology News (GEN) is the world's most widely read biotech publication. It provides the R&D; community with critical information on the tools, technologies, and trends that drive the biotech industry.
Issue link: http://gen.epubxp.com/i/83770
OMICS Gene Expression veiled a serine/arginine protein-specific ki- nase (SRPK)-dependent signal transduction pathway with a central role in regulating al- ternative splicing in mammalian cells. "This is an intriguing research area, be- cause many diseases are known to be caused by defects in splicing regulators, but very few signaling molecules involved in regulated splicing have been characterized to date," says Dr. Fu. Continued from page 37 "In many diseases, even though we can identify the environmental input linked to pathogenesis, we do not know how it con- tributes to the pathological modifications," notes Feng C. Zhou, Ph.D., professor of anatomy, cell biology and neurobiology at the Indiana University School of Medicine. Fetal Alcohol Disorder An interesting example is provided by the fetal alcohol spectrum disorder, a mul- tisystem condition that is causally linked to maternal alcohol use during pregnancy, and is characterized by physical, behavioral, and cognitive deficits, including developmental delay, growth deficiency, craniofacial dys- morphology, and modifications that affect other organs and systems at various degrees. Previously, Dr. Zhou and colleagues re- vealed that ethanol exposure alters the cellu- ™ Magnetic beads Neodymium magnet kDa 75 50 37 25 25 anti-Myc-tag 1 2 kDa 75 50 37 anti-His-tag 1 2 kDa 75 50 37 25 25 20 anti-HA-tag 1 2 kDa 100 75 50 37 anti-RFP 1 2 { International Corporation 38 | October 1, 2012 | genengnews.com | Genetic Engineering & Biotechnology News lar DNA methylation program during early neural tube development, and identified over 2,100 epigenetically changed genes in which the cytosines are differentially methylated in alcohol-treated embryos. To better understand the protein expres- sion changes that occur as a result of epigen- etic and genetic changes in the fetal alcohol spectrum disorder, Dr. Zhou, in collabora- tion with Stephen Mason, Ph.D., an adjunct researcher who is also in the department of anatomy and cell biology at the Indiana University School of Medicine, used whole- embryo cultures to examine the alcohol- signature protein profile across all cell and tissue types in mice at the early neural devel- opmental stage during neurulation. "This study is a continuation of our pre- vious studies," explains Dr. Zhou. The team identified 40 protein spots that were differentially expressed between alco- hol-treated and control cultures. Several of these proteins, confirmed by mass spectrom- etry, fulfill key roles in the cell cycle and the ubiquitin-proteasome pathway. The results indicated that epigenetic and genetic changes occurring as a result of al- cohol exposure impact protein expression during neurulation. The biological functions that were perturbed were linked to tissues and organs that originate, during develop- ment, from all three embryonic layers. "Analyses of epigenetic modifications and those that survey gene expression, protein expression, and metabolic perturbations are required to investigate the molecular and cel- lular changes as a whole, to eventually un- derstand the causal mechanisms that differ between two distinct states, such as between the child with developmental delay caused by drinking during pregnancy and the healthy child," explains Dr. Zhou. "We are trying to understand how gene expression is regulated, how its deregula- tion causes disease, and ultimately how we can correct those deregulated states to treat disease," says Bing Zhang, Ph.D. assistant professor of biomedical informatics at the Vanderbilt University School of Medicine. Dr. Zhang's group has explored the pos- sibility of defining a gene expression signa- ture that can be used to make prognostic and therapeutic decisions in patients with colorec- tal cancer. This malignancy, currently the third leading cause of cancer mortality worldwide, is stratified into four stages (I to IV), with a high- er stage being assigned to more serious disease. Cure, which occurs in approximately 95% of patients with stage I disease treated surgically, is difficult to accomplish in pa- tients with stage IV disease, who also require chemotherapy. "For stage II and III patients, which rep- resent a large population, the question is whether we need to provide chemotherapy, because previous clinical trials suggest that it is not required for certain patients, but it is beneficial for others," explains Dr. Zhang. Histological features, such as tumor size, lymph node positivity, and metastatic dis- semination have been used to perform such predictions in the past, but often they were TECH TIPS