Model developed that predicts molecular response of living cells to genetic or e

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Model developed that predicts molecular response of living cells to

genetic or environmental change

http://www.news-medical.net/?id=33799

Scientists at the Institute for Systems Biology (ISB), in

collaboration with researchers from New York University (NYU), have

developed a model which rapidly characterizes and accurately

predicts the molecular-level, mechanistic response of a free-living

cell to genetic and environmental changes.

The paper describing the EGRIN model was published today in the

online edition of the journal Cell .

The knowledge gained through the Environmental and Gene Regulatory

Influence (EGRIN) model demonstrates that it is possible to discover

how complex biological systems work and opens the door to more

complex genetic engineering that produces fewer unintended

consequences.

Mechanics can fix cars because they know all the parts of a vehicle,

what each part is supposed to do, how the parts are supposed to work

together and what happens when parts wear out over time or stop

functioning due to outside influences. Biologists, on the other

hand, have trouble fixing and/or reengineering cells because they

don ' t have a comprehensive molecular parts list, let alone an

understanding of how those parts work together to facilitate healthy

functioning.

" Unraveling complex biological networks is why I came to ISB, "

said Nitin Baliga, Ph.D., an associate professor at ISB. " The

genomes of more than 500 organisms have been sequenced, yet we as a

scientific community know very little about how their biological

networks function. "

" The systems approach to biology, of which the founders of ISB were

early champions, has proven to be a spectacular success in achieving

a molecular level understanding of complex biology, which is

necessary if we are to engineer cells back to health or reengineer

organisms to improve bioenergy production or bioremediation, for

example, " Baliga said.

The EGRIN model linked biological processes with previously unknown

molecular relationships and accurately predicted both new regulation

of know biological processes and the transcriptional responses of

more than 1,900 genes to completely novel genetic and environmental

experiments.

Baliga and colleagues used Halobacterium salinarum NRC-1 , a member

of the Archaea family of organisms, because it has been the subject

of relatively little scientific study. Archael organisms are

evolutionarily distinct from the two other forms of life, Eukaryotes

and Prokaryotes. They have evolved to thrive in harsh environments

that would be lethal to most other organisms. As a result, their

unique biology could provide new solutions to challenges in

environmental contamination, energy production and healthcare.

Working with an organism about which relatively little is known

allowed the Baliga lab to demonstrate the value of taking a systems

approach, which can lead to the rapid discovery of structure and

function in unstudied biological networks.

" The ability to gather this level of information regarding a poorly

characterized organism from a single study is significant and

unprecedented, " Baliga said. " In addition, the nature of the EGRIN

model is such that it ' s applicable to many complex biological

networks. "

The process of discovery involved perturbing cells (e.g. altering,

individually and in combination, 10 environmental factors and 32

genes), characterizing growth and/or survival phenotype,

quantitatively measuring steady state and dynamic changes in mRNA,

assimilating the changes into a network model able to repeat the

observations and experimentally validating hypotheses formulated

through the model. More than 230 out of 413 microarray experiments

used were collected and/or conducted specifically for this study. In

addition, researchers used data from genome-wide binding location

analysis for eight transcription factors, mass spectrometry-based

proteomic analysis, protein structure predictions, computational

analysis of genome structure and protein evolution as well as data

from public sources.

The vast array of approaches to data gathering and validation

required a systems biology approach, in which scientists of varied

disciplines (e.g. biochemistry, physics, mathematics, computation,

statistics, genetics and more) collaborate and contribute their

skill sets to the achievement of a single scientific objective.

The researchers ' next steps involve applying the EGRIN model to

more complicated organisms and/or networks, and actually

reengineering organisms based on knowledge obtained through the

EGRIN model.

" It will take a lot more effort before the EGRIN model can be

applied in a practical fashion, " Baliga said. " At this point we '

ve basically proven that we can develop a comprehensive

understanding of how complex biological systems work, which has been

an open question to this point. "