Chandra:Systems Biology: Difference between revisions
No edit summary |
No edit summary |
||
| Line 1: | Line 1: | ||
{ChandraLab} | |||
==Introduction== | |||
===Wikipedia Definition=== | |||
Systems biology is an academic field that seeks to integrate different levels of information to understand how biological systems function. By studying the relationships and interactions between various parts of a biological system (e.g. metabolic pathways, organelles, cells, physiological systems, organisms etc.) it is hoped that eventually an understandable model of the whole system can be developed. | Systems biology is an academic field that seeks to integrate different levels of information to understand how biological systems function. By studying the relationships and interactions between various parts of a biological system (e.g. metabolic pathways, organelles, cells, physiological systems, organisms etc.) it is hoped that eventually an understandable model of the whole system can be developed. | ||
--- from Wikipedia | --- from Wikipedia | ||
The systems approach is not new, even to biology. However, the level of abstraction has changed phenomenally in the post-genomic era, with the explosion of data. Also, the complexity of the system was discouraging in the past, which has now been dispelled to an extent with the development of powerful computational techniques. The response of systems to ''perturbations'' (natural, such as SNPs and mutagenesis) as well as introduction of a drug is of particular interest in systems biology. | |||
==Our Work== | |||
At the Chandra lab, we look to address the problem of drug discovery from a systems perspective. Systems biology, in drug discovery, promises to identify newer drug targets and identify more efficacious drugs, with fewer side effects. Metabolic analysis is of immense importance in drug design, quoting Cornish-Bowden: | At the Chandra lab, we look to address the problem of drug discovery from a systems perspective. Systems biology, in drug discovery, promises to identify newer drug targets and identify more efficacious drugs, with fewer side effects. Metabolic analysis is of immense importance in drug design, quoting Cornish-Bowden: | ||
"... what cells do is metabolism and a major thing drugs are supposed to do is to alter metabolism: of the 500 current targets, | "... what cells do is metabolism and a major thing drugs are supposed to do is to alter metabolism: of the 500 current targets, | ||
30% are enzymes and 45% are receptors. To forget metabolism when discussing strategies for drug design or drug discovery is a | 30% are enzymes and 45% are receptors. To forget metabolism when discussing strategies for drug design or drug discovery is a | ||
mistake. | mistake." | ||
– Athel Cornish-Bowden and María Luz Cárdenas | – Athel Cornish-Bowden and María Luz Cárdenas | ||
C. R. Biologies (2003) 326:509–515 '''PMID 12886878''' | ''C. R. Biologies'' (2003) '''326''':509–515 '''PMID 12886878''' | ||
We have applied Flux Balance Analysis (FBA) and Minimisation of Metabolic Adjustment (MoMA) for the analysis of the ''Mycobacterium tuberculosis'' mycolic acid biosynthesis pathway and identified six new potential drug targets based on this analysis. Systems biology affords the modelling of systems at various hierarchies to make appropriate predictions and form hypotheses. | |||
==Further Reading== | |||
*Covert MW, Schilling CH, Famili I, Edwards JS, Goryanin II, Selkov E and Palsson BØ. "Metabolic modeling of microbial strains ''in silico''". ''Trends in Biochemical Sciences'', '''26''':179–186, 2001. '''PMID 11246024''' | |||
*Edwards JS, Covert M, Palsson BØ. "Metabolic modelling of microbes: the flux-balance approach". ''Environmental Microbiology'' '''4''':133–140, 2002. '''PMID 12000313''' | |||
*Segrè D, Vitkup D and Church GM. "Analysis of optimality in natural and perturbed metabolic networks". ''Proceedings of the National Academy of Sciences, USA'', '''99''':15112–15117, 2002. '''PMID 12415116''' | |||
*Voit EO. Computational Analysis of Biochemical Systems. Cambridge University Press, Cambridge, UK, 2000. '''[http://www.amazon.com/gp/product/0521785790/ ISBN:0521785790] | |||
Revision as of 09:12, 19 December 2005
{ChandraLab}
Introduction
Wikipedia Definition
Systems biology is an academic field that seeks to integrate different levels of information to understand how biological systems function. By studying the relationships and interactions between various parts of a biological system (e.g. metabolic pathways, organelles, cells, physiological systems, organisms etc.) it is hoped that eventually an understandable model of the whole system can be developed. --- from Wikipedia
The systems approach is not new, even to biology. However, the level of abstraction has changed phenomenally in the post-genomic era, with the explosion of data. Also, the complexity of the system was discouraging in the past, which has now been dispelled to an extent with the development of powerful computational techniques. The response of systems to perturbations (natural, such as SNPs and mutagenesis) as well as introduction of a drug is of particular interest in systems biology.
Our Work
At the Chandra lab, we look to address the problem of drug discovery from a systems perspective. Systems biology, in drug discovery, promises to identify newer drug targets and identify more efficacious drugs, with fewer side effects. Metabolic analysis is of immense importance in drug design, quoting Cornish-Bowden:
"... what cells do is metabolism and a major thing drugs are supposed to do is to alter metabolism: of the 500 current targets,
30% are enzymes and 45% are receptors. To forget metabolism when discussing strategies for drug design or drug discovery is a
mistake."
– Athel Cornish-Bowden and María Luz Cárdenas
C. R. Biologies (2003) 326:509–515 PMID 12886878
We have applied Flux Balance Analysis (FBA) and Minimisation of Metabolic Adjustment (MoMA) for the analysis of the Mycobacterium tuberculosis mycolic acid biosynthesis pathway and identified six new potential drug targets based on this analysis. Systems biology affords the modelling of systems at various hierarchies to make appropriate predictions and form hypotheses.
Further Reading
- Covert MW, Schilling CH, Famili I, Edwards JS, Goryanin II, Selkov E and Palsson BØ. "Metabolic modeling of microbial strains in silico". Trends in Biochemical Sciences, 26:179–186, 2001. PMID 11246024
- Edwards JS, Covert M, Palsson BØ. "Metabolic modelling of microbes: the flux-balance approach". Environmental Microbiology 4:133–140, 2002. PMID 12000313
- Segrè D, Vitkup D and Church GM. "Analysis of optimality in natural and perturbed metabolic networks". Proceedings of the National Academy of Sciences, USA, 99:15112–15117, 2002. PMID 12415116
- Voit EO. Computational Analysis of Biochemical Systems. Cambridge University Press, Cambridge, UK, 2000. ISBN:0521785790
