Biomedical subjects

Pawan K Dhar

Publications and source records attributed to Pawan K Dhar.

5 recordsLinked to original sources

PubMed2006

Metabolic pathways variability and sequence/networks comparisons.

BACKGROUND: In this work a simple method for the computation of relative similarities between homologous metabolic network modules is presented. The method is similar to classical sequence alignment and allows for the generation of phenotypic trees amenable to be compared with correspondent sequence based trees. The procedure can be applied to both single metabolic modules and whole metabolic network data without the need of any specific assumption. RESULTS: We demonstrate both the ability of the proposed method to build reliable biological classification of a set of microorganisms and the strong correlation between the metabolic network wiring and involved enzymes sequence space. CONCLUSION: The method represents a valuable tool for the investigation of genotype/phenotype correlations allowing for a direct comparison of different species as for their metabolic machinery. In addition the detection of enzymes whose sequence space is maximally correlated with the metabolic network space gives an indication of the most crucial (on an evolutionary viewpoint) steps of the metabolic process.

Algorithms↗

PubMed2006

Transient block of receptor may be a mechanism controlling unidirectional propagation of signaling.

In tissue development, juxtacrine signaling often propagates across cells, carrying and delivering temporal and spatial information for cells to make correct patterning. Observed complex and accurate tissue patterning indicates that signaling propagation via ligand-receptor interactions is precisely controlled. It is important and interesting to reveal the possible control mechanisms. The directionality of signaling in cells, which is a common issue for all intercellular signaling pathways, is a critical aspect. To understand the propagation of Notch signaling in presomitic mesoderm cells in the mouse, a novel method is used to build a multicellular model to simulate Notch signaling. Simulation reveals that the transient block of Notch by Notch induced Lfng and the delayed removal of the block by another Notch induced protein Hes7 may explain the observed unidirectional propagation of Notch signaling in these cells. Both mutation in and overexpression of lfng cause the same signaling profile in the tissue, due to the inappropriate timing of Notch signaling block by Lfng. The reverse Notch/Delta signaling quickly develops into reciprocating signaling among cells, causing irregular expression of cyclic genes. Irregular Notch signaling in cells would change their response to the positional information provided by the Fgf8 gradient, resulting in disordered and irregular somite segmentation. As Notch signaling is highly conserved, we hypothesize that the mechanism of controlling unidirectional propagation of signaling in cells by transient receptor block may exist in other tissues and in other vertebrates. Our simulation results also suggest that segmentation clock and unidirectional propagation may be inherently coupled in Notch signaling.

Animals↗

PubMed2005

Bone and the kidney: a systems biology approach to the molecular mechanisms of renal osteodystrophy.

Despite its apparent static condition, the skeleton undergoes a permanent process of remodeling mediated by osteoblasts and osteoclasts. The activity of these cells is regulated by a plethora of factors, ranging from mechanical stress to the effects of hormones to the immune system. One well-studied regulatory system involves the maintenance of calcium homeostasis through a network whose main regulatory components include ionized calcium, phosphate, parathyroid hormone and active vitamin D. This system establishes the link between bone and kidney, as one of the kidney's endocrine functions is the activation of vitamin D, while electrolyte homeostasis is one of its excretory functions. Impaired renal function leads to disturbances in this regulatory system, resulting in the complex syndrome of renal osteodystrophy that affects the majority of patients with chronic renal failure. This review summarizes the current understanding of bone physiology on a molecular level, examines some of the pathological pathways related to renal disease, and concludes with an outlook on how the emerging field of systems biology may contribute to a more dynamic and quantitative understanding of the physiology and pathophysiology of renal bone disease.

Animals↗

PubMed2004

Grid cellware: the first grid-enabled tool for modelling and simulating cellular processes.

Modelling and simulation of complex cellular transactions involve development of platforms that understand diverse mathematical representations and are capable of handling large backend computations. Grid Cellware, an integrated modelling and simulation tool, has been developed to precisely address these niche requirements of the modelling community. Grid Cellware implements various pathway simulation algorithms along with adaptive Swarm algorithm for parameter estimation. For enchanced computational productivity Grid Cellware uses grid technology with Globus as the middleware.

Algorithms↗

PubMed2004

Computational approach to systems biology: from fraction to integration and beyond.

Systems biology is an approach to understanding the workings of whole biological systems. The various methods used for systems analyses range from experimental to computational. In this paper, we describe basic concepts of systems biology, modeling challenges that arise from the massively parallel interaction among components in biological systems, and what lies beyond integration of modular knowledge.

Animals↗