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57 results on '"Gutteridge, Alex"'

56. Nutrient control of eukaryote cell growth: asystems biology study in yeast.

Author

Gutteridge, Alex, Pir, Pinar, Castrillo, Juan I., Charles, Philip D., Lilley, Kathryn S., and Oliver, Stephen G.

Subjects
EUKARYOTIC cells, GENETIC regulation, SYSTEMS biology, YEAST, PLANT nutrients
Abstract

Background: To elucidate the biological processes affected by changes in growth rate and nutrient availability, we have performed a comprehensive analysis of the transcriptome, proteome and metabolome responses of chemostat cultures of the yeast, Saccharomyces cerevisiae, growing at a range of growth rates and in four different nutrient-limiting conditions. Results: We find significant changes in expression for many genes in each of the four nutrient-limited conditions tested. We also observe several processes that respond differently to changes in growth rate and are specific to each nutrient-limiting condition. These include carbohydrate storage, mitochondrial function, ribosome synthesis, and phosphate transport. Integrating transcriptome data with proteome measurements allows us to identify previously unrecognized examples of post-transcriptional regulation in response to both nutrient and growth-rate signals. Conclusions: Our results emphasize the unique properties of carbon metabolism and the carbon substrate, the limitation of which induces significant changes in gene regulation at the transcriptional and post-transcriptional level, as well as altering how many genes respond to growth rate. By comparison, the responses to growth limitation by other nutrients involve a smaller set of genes that participate in specific pathways. See associated commentary http://www.biomedcentral.com/1741-7007/8/62 [ABSTRACT FROM AUTHOR]

Published
2010
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57. Phenome-wide Mendelian randomization mapping the influence of the plasma proteome on complex diseases

Author

Zheng, Jie, Haberland, Valeriia, Baird, Denis, Walker, Venexia, Haycock, Philip C, Hurle, Mark R, Gutteridge, Alex, Erola, Pau, Liu, Yi, Luo, Shan, Robinson, Jamie, Richardson, Tom G, Staley, James R, Elsworth, Benjamin, Burgess, Stephen, Sun, Benjamin B, Danesh, John, Runz, Heiko, Maranville, Joseph C, Martin, Hannah M, Yarmolinsky, James, Laurin, Charles, Holmes, Michael V, Liu, Jimmy Z, Estrada, Karol, Santos, Rita, McCarthy, Linda, Waterworth, Dawn, Nelson, Matthew R, Smith, George Davey, Butterworth, Adam S, Hemani, Gibran, Scott, Robert A, and Gaunt, Tom R

Subjects
Phenotype, Proteome, Humans, Genetic Predisposition to Disease, Blood Proteins, Mendelian Randomization Analysis, Polymorphism, Single Nucleotide, 3. Good health, Genome-Wide Association Study
Abstract

The human proteome is a major source of therapeutic targets. Recent genetic association analyses of the plasma proteome enable systematic evaluation of the causal consequences of variation in plasma protein levels. Here we estimated the effects of 1,002 proteins on 225 phenotypes using two-sample Mendelian randomization (MR) and colocalization. Of 413 associations supported by evidence from MR, 130 (31.5%) were not supported by results of colocalization analyses, suggesting that genetic confounding due to linkage disequilibrium is widespread in naïve phenome-wide association studies of proteins. Combining MR and colocalization evidence in cis-only analyses, we identified 111 putatively causal effects between 65 proteins and 52 disease-related phenotypes ( https://www.epigraphdb.org/pqtl/ ). Evaluation of data from historic drug development programs showed that target-indication pairs with MR and colocalization support were more likely to be approved, evidencing the value of this approach in identifying and prioritizing potential therapeutic targets.

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