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Biomedical subjects

B Palsson

Publications and source records attributed to B Palsson.

6 recordsLinked to original sources
PubMed2001

Regulation of gene expression in flux balance models of metabolism.

Genome-scale metabolic networks can now be reconstructed based on annotated genomic data augmented with biochemical and physiological information about the organism. Mathematical analysis can be performed to assess the capabilities of these reconstructed networks. The constraints-based framework, with flux balance analysis (FBA), has been used successfully to predict time course of growth and by-product secretion, effects of mutation and knock-outs, and gene expression profiles. However, FBA leads to incorrect predictions in situations where regulatory effects are a dominant influence on the behavior of the organism. Thus, there is a need to include regulatory events within FBA to broaden its scope and predictive capabilities. Here we represent transcriptional regulatory events as time-dependent constraints on the capabilities of a reconstructed metabolic network to further constrain the space of possible network functions. Using a simplified metabolic/regulatory network, growth is simulated under various conditions to illustrate systemic effects such as catabolite repression, the aerobic/anaerobic diauxic shift and amino acid biosynthesis pathway repression. The incorporation of transcriptional regulatory events in FBA enables us to interpret, analyse and predict the effects of transcriptional regulation on cellular metabolism at the systemic level.

Amino Acids↗
PubMed1999

A genome-wide scan reveals a maternal susceptibility locus for pre-eclampsia on chromosome 2p13.

Pre-eclampsia is a common and serious disease and a major cause of maternal and infant mortality. Antenatal care systems world-wide screen for signs of the disease such as hypertension and proteinuria. Unlike most other human disorders it impacts two individuals, the mother and the child, both of whom can be severely affected. The pathophysiology of the disorder is incompletely understood, but familial clustering of the disease is apparent. Here we report the results of a genome-wide screen of Icelandic families representing 343 affected women. Including those patients with non-proteinuric pre-eclampsia (gestational hypertension), proteinuric pre-eclampsia and eclampsia, we detected a significant locus on 2p13 with a lod score of 4.70 (single point P < 3.49 x 10(-6)). This is the first reported locus for pre-eclampsia meeting the criteria for genome-wide significance.

Chromosome Mapping↗
PubMed1997

The physico-chemical factors that govern retrovirus-mediated gene transfer.

The most commonly used vehicle for gene transfer into human target cells is a replication incompetent retroviral vector. The efficiency of gene transfer with this type of vector has proven to be too low to implement effective gene therapy. To date much effort has gone into engineering the genetic and biochemical functionalities of retroviral vectors. Although progress has been achieved, high-efficiency reproducible gene transfer into human cells remains elusive. There are many important physico-chemical and systemic kinetic factors that govern the process of retrovirus-mediated gene transfer. These factors have gone mostly unrecognized to date. The former include the nature of the random Brownian motion of the retrovirus and the physico-chemical forces that determine the binding of the retroviral vector to the target cell. The latter arise from the kinetics of virus binding and entry into the target cell, as well as the kinetic interplay between cell-cycle and retroviral life-cycle events that determine the intracellular fate of the virus. This review describes these processes and how they constrain the efficiency of the gene transfer process.

Animals↗
PubMed1981

Determination of steady state generation time distributions from labelled mitosis experimental data.

The proper application of detailed deterministic cell kinetic models depends on the way in which cells are assigned their generation times. A method is presented for the determination of population generation time distributions from labelled mitoses experiments. The model assumes that the generation time of each new cell is a function of both the steady-state generation time distribution function of the population, and also the generation time frequency-function of the previous generation of cells. This approach is applied to two different cell types to successfully simulate extended labelled mitoses curves using a population balance model with constant maturation rates.

Animals↗