Molecular Genomics / DNA Oligo Synthesis
Hair follicles in the scalp of mammals, including humans, are intimately associated with and responsible for the production of scalp proteins such as elastin. The elastin fibers in the upper dermis are exclusively synthesized by the cells lining the root sheath in the hair follicle1. This establishes an intimate connection between the hair follicles and the extracellular matrix that supports the follicles in the skin. There is growing evidence that other reasons, including damage to the proteins in the scalp from sunlight and environmental factors also cause thinning and loss of hair. This is a self-reinforcing problem, because as hair thins and becomes more sparse, greater amounts of sunlight, in particular in the UV range of the spectrum, can penetrate to the scalp and damage the proteins in the scalp matrix. For example, there are significant difference between the elastin in the scalp of infants compared to adults. Figure 1 shows an elastin-stained section of skin from the scalp of a human infant, displaying organized bundles of elastin associated with the hair follicle2 (HF).
DNA/RNA Synthesis; DNA Sequencing; Gene Synthesis; ..
TCAG focuses largely on projects concerned with whole genome sequencing data, and maintains core facilities for: DNA sequencing and synthesis; cytogenomics and genome resources; microarray analysis and gene expression; genetic and statistical analysis; and biobanking and databases.
In processes where genes are known to be involved, the mouse provides an extensive toolkit to investigate their action in more detail?. For example, the relative contribution of components of insulin signaling pathways, glucose uptake and insulin resistance have been studied via the generation of global or tissue-specific knockouts. A global homozygous knockout of the insulin receptor in mouse leads to fatal ketoacidosis in neonates; however, heterozygotes exhibit mild hyperglycemia with a corresponding hyperinsulinemia with some 10% of adult mice eventually developing diabetes dependent on background strain (Accili et al., 1996). A number of tissue-specific insulin receptor knockouts were generated using the Cre/loxP system and they have elucidated some of the complex interactions between various tissues during the development of impaired glucose tolerance and type 2 diabetes (summarized in Table 1). Surprisingly, muscle specific insulin receptor knockout (MIRKO) mice appeared to have normal glucose tolerance although insulin-stimulated muscle glucose uptake and glycogen synthesis were severely impaired accompanied by an increase in insulin-stimulated glucose transport in fat (Bruning, 1998; Kim et al., 2000). In addition, MIRKO mice have elevated fat deposits, serum triglycerides, and free fatty acid levels; thus, insulin resistance in muscle leads to dislipidemia and obesity but not to diabetes. Liver-specific insulin receptor knockout (LIRKO) in contrast exhibited severe insulin resistance, glucose intolerance and a failure of insulin to suppress hepatic glucose production (Michael et al., 2000). Mice additionally had marked hyperinsulinemia and an almost sixfold increase in j-cell mass. j-cell insulin receptor knockout jIRKO) mice lack glucose induced first phase insulin release and develop glucose intolerance with age (Kulkarni et al., 1999).
The first synthesis of an artificial gene
The Affymetrix technology is based on targets hybridization with oligonucleotides synthetized directly on arrays by photolithography. Arrays contain hundreds of thousands of oligonucleotide probes packed at extremely high densities.
Defects in cholesterol synthesis genes in mouse …
Further support for the idea that elastin structure in the scalp is linked to and supports hair growth is provided by a mouse genetic model called rough coat4. Mice with the rough coat genetic defect have significantly reduced levels and altered deposition of both elastin and collagen in their skin and internal organs. Rough coat mice also display progressive hair loss -- similar to male pattern baldness in humans. These observations strongly suggest that the protein elastin is both synthesized by and essential for the complete functioning of hair follicles. Elastin damage by aging processes and sunlight contribute to the loss and thinness of hair as we age.
Gene Synthesis Applications in Cancer Biology on Thursday, ..
Metabolism1.0 Global and overview maps1.1 Carbohydrate metabolism1.2 Energy metabolism1.3 Lipid metabolism1.4 Nucleotide metabolism1.5 Amino acid metabolism1.6 Metabolism of other amino acids1.7 Glycan biosynthesis and metabolism1.8 Metabolism of cofactors and vitamins1.9 Metabolism of terpenoids and polyketides1.10 Biosynthesis of other secondary metabolites1.11 Xenobiotics biodegradation and metabolism1.12 Chemical structure transformation maps
Photochemic synthesis of a DNA probe in ..
Submissions from 2014. Amoroso, Jon William (2014) Reactive Probes for Manipulating Polyketide Synthases, and Photoreactive Probes for Strained Alkyne Click Chemistry