The Scripps Research Institute is a nonprofit American medical research facility that focuses on research and education in the biomedical science. Headquartered in San Diego, California with a sister facility in Jupiter, Florida, the institute is home to 3,000 scientists, technicians, graduate students, and administrative and other staff, making it among the largest private, non-profit biomedical research organizations in the world. Wikipedia.
Dyson H.J.,Scripps Research Institute
Quarterly Reviews of Biophysics
Proteins provide much of the scaffolding for life, as well as undertaking a variety of essential catalytic reactions. These characteristic functions have led us to presuppose that proteins are in general functional only when well structured and correctly folded. As we begin to explore the repertoire of possible protein sequences inherent in the human and other genomes, two stark facts that belie this supposition become clear: firstly, the number of apparent open reading frames in the human genome is significantly smaller than appears to be necessary to code for all of the diverse proteins in higher organisms, and secondly that a significant proportion of the protein sequences that would be coded by the genome would not be expected to form stable three-dimensional (3D) structures. Clearly the genome must include coding for a multitude of alternative forms of proteins, some of which may be partly or fully disordered or incompletely structured in their functional states. At the same time as this likelihood was recognized, experimental studies also began to uncover examples of important protein molecules and domains that were incompletely structured or completely disordered in solution, yet remained perfectly functional. In the ensuing years, we have seen an explosion of experimental and genome-annotation studies that have mapped the extent of the intrinsic disorder phenomenon and explored the possible biological rationales for its widespread occurrence. Answers to the question 'why would a particular domain need to be unstructured?' are as varied as the systems where such domains are found. This review provides a survey of recent new directions in this field, and includes an evaluation of the role not only of intrinsically disordered proteins but also of partially structured and highly dynamic members of the disorder-order continuum. © 2011 Cambridge University Press. Source
Karbstein K.,Scripps Research Institute
Trends in Cell Biology
Protein synthesis on ribosomes is carefully quality-controlled to ensure the faithful transmission of genetic information from mRNA to protein. Many of these mechanisms rely on communication between distant sites on the ribosomes, and thus on the integrity of the ribosome structure. Furthermore, haploinsufficiency of ribosomal proteins, which increases the chances of forming incompletely assembled ribosomes, can predispose to cancer. Finally, release of inactive ribosomes into the translating pool will lead to their degradation together with the degradation of the bound mRNA. Together, these findings suggest that quality control mechanisms must be in place to survey nascent ribosomes and ensure their functionality. This review gives an account of these mechanisms as currently known. © 2013 Elsevier Ltd. Source
Kenny P.,Scripps Research Institute
Food is consumed in order to maintain energy balance at homeostatic levels. In addition, palatable food is also consumed for its hedonic properties independent of energy status. Such reward-related consumption can result in caloric intake exceeding requirements and is considered a major culprit in the rapidly increasing rates of obesity in developed countries. Compared with homeostatic mechanisms of feeding, much less is known about how hedonic systems in brain influence food intake. Intriguingly, excessive consumption of palatable food can trigger neuroadaptive responses in brain reward circuitries similar to drugs of abuse. Furthermore, similar genetic vulnerabilities in brain reward systems can increase predisposition to drug addiction and obesity. Here, recent advances in our understanding of the brain circuitries that regulate hedonic aspects of feeding behavior will be reviewed. Also, emerging evidence suggesting that obesity and drug addiction may share common hedonic mechanisms will also be considered. © 2011 Elsevier Inc. Source
Topol E.J.,Scripps Research Institute
That each of us is truly biologically unique, extending to even monozygotic, "identical" twins, is not fully appreciated. Now that it is possible to perform a comprehensive "omic" assessment of an individual, including one's DNA and RNA sequence and at least some characterization of one's proteome, metabolome, microbiome, autoantibodies, and epigenome, it has become abundantly clear that each of us has truly one-of-a-kind biological content. Well beyond the allure of the matchless fingerprint or snowflake concept, these singular, individual data and information set up a remarkable and unprecedented opportunity to improve medical treatment and develop preventive strategies to preserve health. © 2014 Elsevier Inc. Source
Scripps Research Institute | Date: 2015-04-27
The present invention provides novel substituted pyrimidinyl-amines that are useful as inhibitors of protein kinases, especially c-Jun N-terminal kinases (JNK) and pharmaceutical compositions thereof and methods of using the same for treating conditions responsive to the inhibition of the JNK pathway.