Dr. Doriano Brogioli

Effect of intercalators and groove binders on DNA tensional and torsional properties

 

ABSTRACT: We study the mechanical properties of single DNA molecules by using two complementary techniques: AFM imaging and magnetic tweezers manipulation. Both the techniques allow to measure contour and persistence length. Moreover, magnetic tweezers allow to measure the torsional properties. Here, we present results concerning the effect of drugs on DNA molecules: we studied intercalators (ethidium bromide, doxorubicin), and minor groove binder (netropsin). We are able to detect the effects in terms of change in contour length, elasticity, induced torsion, denaturation, strand breaks, for each drug. For what concerns intercalators, we are able to quantify their effects in terms of DNA length and flexibility increase and reduction in twist per base. We observed that doxorubicin has peculiar effects: it induces strand breaks and molecule collapse. We also show elusive hysteresis effects both on tensional and torsional properties. We are also able to quantify the twist per base increase induced by the minor groove binder netropsin.

 

BIO: Dr. Brogioli works as a researcher in a group of bio-physicists at the Experimental Medicine department of Universita' degli Studi di Milano-Bicocca.  She receive her Ph. D. in Physics (2002), with a thesis titled "Near Field Speckles".  Her Research experience includes
- DNA mechanical properties and the effects of drugs
- in-vitro study of aggregation processes of amyloid beta peptides
- development of optical devices for the study of nanoparticles, colloids and aggregation

Her research interests include the development of innovative instruments for the investigation of nano or micron scale world. Along this line, she developed optical techniques, [see for example "Near-field intensity correlations of scattered light", Appl. Opt. 40 (24), 4036-4040  (2001)] and techniques for the measurement of mechanical properties of single molecules [see for example "Tethered particle motion as a diagnostic of DNA tether length", J. Phys.
Chem. B, 110 (34), 17260-17267 (2006)], including the so-called magnetic tweezers. Investigated phenomena include non-equilibrium fluctuations in fluids [see  "Diffusive mass transfer by nonequilibrium fluctuations: Fick's law revisited", Phis. Rev. E 63 (1) (2001), colloids, bio-physical systems [see for example "Tethered particle motion as a diagnostic of DNA tether length", J. Phys. Chem. B, 110 (34), 17260-17267 (2006)] and electrokinetic problems [see "Extracting renewable energy from a salinity difference using a capacitor.", Phys. Rev. Lett. 103, 058501-1-4 (2009)].

 

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