3 Bullets SWATH mass spectrometry, an emerging protein analysis technique being pioneered by ISB researchers, provides a digital fingerprint of all accessible proteins in a sample. The data generated by the SWATH technique are highly complex and require sophisticated computational tools in order to extract identities from a sea of data. ISB researchers have released a free, open source program that allows users to confidently identify and quantify proteins analyzed…
3 Bullets: The barrier function of skin is integral to personal well-being and is associated with several widespread diseases such as eczema and psoriasis. ISB and Procter & Gamble researchers used human skin grown in the lab to measure changes in protein levels as the skin matures. The results of this study provide many new markers for healthy skin development. By Dr. Kristian Swearingen and Dr. Jason Winget In a…
3 Bullets: Inflammation causes cholesterol buildup and leads to cardiovascular disease, the leading cause of death in the world ISB, Seattle Biomed, and Oregon State University researchers collaborate to identify a compendium of proteins that control expression of a key regulator of cholesterol efflux Targeting cholesterol efflux to HDL is a potentially important therapeutic strategy for preventing and treating cardiovascular disease By Dr. Mark Gillespie Cells of the immune system,…
3 Bullets: Bipolar disorder (BD) is a common, severe and recurrent psychiatric disorder with no known cure and substantial morbidity and mortality. Heritable causes contribute up to 80 percent of lifetime risk for BD. Scientists hope that identifying the specific genes involved in risk for bipolar disorder will lead to new ways to treat the disease. ISB researchers identified contributions of rare variants to BD by sequencing the genomes of…
3 Bullets: Kaviar is ISB’s comprehensive catalog of human genomic variation Kaviar combines 31 data sources for a total of 151 million single nucleotide variants (SNVs), covering 5% of all the positions in the human genome A researcher studying possible disease-causing variants can use Kaviar to answer the question, “Have these variants been observed before, and if so, how often?” By Terry Farrah A typical pair of human genomes are…
3 Bullets: ISB researchers used a data-driven mathematical model to identify specific genes associated with hair regeneration Novel methodology paves way for continued research into the molecular basis of this complex cycle as well as other regenerative organs like skin and liver Findings may lead to more precise targets for therapies and genetic markers of hair wellness By Varsha Dhankani Scientists at ISB have identified genes associated with the growth-and-death…
3 Bullets: Mycobacterium tuberculosis (MTB) infects more than 1.5 billion people worldwide partly due to its ability to sense and adapt to the broad range of hostile environments that exist within hosts. To study how MTB controls its responses at a molecular level, ISB researchers and their collaborators at Seattle Biomed perturbed almost all MTB transcription factor regulators and identified the affected genes. This comprehensive map of molecular switches in…
3 Bullets: Proteomics experiments generate huge amounts of raw data, most of which cannot be easily shared or described in a publication. ISB researchers curate publicly accessible databases that allow researchers to share their data with the world and to use data others have collected. All data are analyzed in a consistent manner and results are presented via searchable, user-friendly web applications. By Dr. Kristian Swearingen Institute for Systems Biology…
3 Bullets: When an organism duplicates its genes, it increases its ability to adapt and colonize new environments. ISB researchers used the systems approach to study how one family of microbial genes evolved to bring functions that were adaptive to specific environments. This new understanding of how gene regulatory networks rewire themselves has many potential applications, including how to wire new functions into an organism for biofuel production, bio-remediation or…
3 Bullets: ‘Big data’ cancer research has revealed a new spectrum of genetic mutations across tumors that need understanding. Existing methods for analyzing DNA defects in cancer are blind to how those mutations actually behave. ISB scientists developed a new approach using physics- and structure-based modeling to systematically assess the spectrum of mutations that arise in several gene regulatory proteins in cancer. By Jake Valenzuela and Justin Ashworth A significant…
3 Bullets: Dengue virus is the most prevalent mosquito-borne virus worldwide, infecting an estimated 400 million people per year and causing about 25,000 deaths. It’s necessary to understand the molecular mechanisms of dengue replication in order to develop an effective treatment. Researchers at ISB and Seattle BioMed developed a novel approach for identifying host proteins that associate with dengue replication machinery. By Thurston Herricks Dengue virus (DENV) infects approximately 400…
3 Bullets: The Institute for Systems Biology and Seattle BioMed have collaborated to reconstruct the gene regulatory network of the human pathogen Mycobacterium tuberculosis. Finely tuned gene regulation has allowed Mycobacterium tuberculosis to survive unnoticed in an apparently healthy host for decades; understanding those subtleties is critical for advancing treatment. The identification of co-regulated sets of genes and their regulatory influences offers validated predictions that will help guide future research…
3 Bullets: Adams-Oliver syndrome (AOS) is a rare congenital disease characterized by scalp lesions and limb defects. Additional vascular abnormalities and heart defects can lead to early death in some patients. By analyzing twelve families affected with the disease, we identified causal mutations in a new disease gene, NOTCH1, in five families. NOTCH1 is likely to be the major cause of AOS. NOTCH1 codes for a transcription factor that governs…
3 Bullets: Aggressive tumor growth is linked to high activity of a macromolecular assembly called RNA polymerase I. ISB and FHCRC researchers collaborate to map the architecture of the assembly using a powerful crosslinking-mass spectrometry (CXMS) technology. Structural maps provide important insights into therapeutic targets for cancer treatment. By Mark Gillespie Rapidly growing tumor cells require large amounts of protein for their survival. This increased protein synthesis, or translation, can…
3 Bullets: Computer simulation is a promising way to model multicellular biological systems to help understand complexity underlying health and disease. Biocellion is a high-performance computing (HPC) framework that enables the simulation of billions of cells across multiple scales. Biocellion facilitates researchers without HPC expertise to easily build and simulate large models. By Theo Knijnenburg How do molecular changes, such as a mutation in the DNA or infection by a…
3 Bullets: Gastric cancer has a high mortality rate, but current classification systems haven’t been effective in helping to identify subtypes relevant for treatment of the disease. TCGA researchers have integrated molecular data from 295 stomach tumors and have discovered four subtypes of gastric cancer. Stratification of patients into these four subtypes paves the way for the development of new personalized therapies. By Theo Knijnenburg Gastric cancer is among the…
3 Bullets: Institute for Systems Biology and Seattle BioMed researchers collaborated and discovered a new protein post-translational modification in the human pathogen Mycobacterium tuberculosis. Post-translational modifications are essential mechanisms used by cells to diversify protein functions and ISB scientists identified the rare phosphorylated tyrosine post translational modification on Mycobacterium tuberculosis proteins using mass spectrometry. Inhibiting phosphotyrosine modified amino acids in Mycobacterium tuberculosis severely limits the growth of this widespread deadly…
(Photo above: ISB’s Dr. Ilya Shmulevich describes his lab’s work in The Cancer Genome Atlas project and how ISB and FHCRC could collaborate.) Big health challenges require big science. Cancers are prime examples of overwhelmingly complex diseases that need the power of a cross-disciplinary, systems biology approach to decipher the underlying dysfunctional gene networks in order to find ways to prevent and manage the diseases and develop more effective therapies….
