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SUMMARY:Sibling Rivalry and Stress Tolerance: the Single-Cell Biology of M
 ycobacteria. - Dr Bree Aldridge\, Tufts University\, Department of Molecul
 ar Biology and Microbiology\,  Boston 
DTSTART:20130606T133000Z
DTEND:20130606T143000Z
UID:TALK44446@talks.cam.ac.uk
CONTACT:Caroline Newnham
DESCRIPTION:Mycobacterium tuberculosis infects billions of people worldwid
 e and kills more than 1.5 million per year. TB remains extremely difficult
  to treat with antibiotics\, requiring months to years of therapy for cure
 . The variable course of disease and treatment response suggests that func
 tionally heterogeneous populations of mycobacteria respond differently str
 ess. Using a quantitative single-cell approach\, we show that mycobacteria
  deterministically generate diversity in their growth characteristics thro
 ugh an asymmetric growth pattern. Coupled with a cell cycle regulated by t
 ime and not size\, this asymmetry creates subpopulations of cells with dis
 tinct growth rates and cell sizes that are differentially susceptible to c
 linically relevant classes of antibiotics. Thus\, the unusual growth patte
 rn intrinsic to mycobacteria deterministically creates a diverse populatio
 n structure that may underlie phenotypes previously thought to be controll
 ed by external stressors. We have also observed variation among microcolon
 ies in antibiotic susceptibility that cannot be explained by growth pole a
 ge. We have established markers of cell cycle state to test the hypothesis
  that cell cycle state is another determinant of drug susceptibility. Arme
 d with new image analysis algorithms\, reporters of cell state\, and mathe
 matical models\, we seek to quantitatively characterize and pharmacologica
 lly target drug tolerant mycobacterial subpopulations. 
LOCATION:Part II Room\, Department of Genetics
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