Improved network performance via antagonism: From synthetic rescues to multi-drug combinations

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

Abstract

Recent research shows that a faulty or sub-optimally operating metabolic network can often be rescued by the targeted removal of enzyme-coding genes - the exact opposite of what traditional gene therapy would suggest. Predictions go as far as to assert that certain gene knockouts can restore the growth of otherwise nonviable gene-deficient cells. Many questions follow from this discovery: What are the underlying mechanisms? How generalizable is this effect? What are the potential applications? Here, I approach these questions from the perspective of compensatory perturbations on networks. Relations are drawn between such synthetic rescues and naturally occurring cascades of reaction inactivation, as well as their analogs in physical and other biological networks. I specially discuss how rescue interactions can lead to the rational design of antagonistic drug combinations that select against resistance and how they can illuminate medical research on cancer, antibiotics, and metabolic diseases.

Original languageEnglish (US)
Pages (from-to)236-245
Number of pages10
JournalBioEssays
Volume32
Issue number3
DOIs
StatePublished - Mar 2010

Keywords

  • Antagonistic interactions
  • Biological networks
  • Cascade control
  • Cellular metabolism

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Fingerprint Dive into the research topics of 'Improved network performance via antagonism: From synthetic rescues to multi-drug combinations'. Together they form a unique fingerprint.

Cite this