Dr. Guy Nir: From BINA to Harvard Medical School

Watson and Crick’s discovery of the double-helix in 1953 made it easy for non-scientists to visualize DNA structure. But within the watery world of the living cell, DNA molecules – and the proteins with which they interact – undergo constant, dynamic change. Dr. Guy Nir, a BIU alumnus who completed his PhD under BINA Director Prof. Yuval Garini and is now a post-doctoral researcher at Harvard Medical School, is creating advanced fluidic techniques that allow us to observe and analyze these conformational changes as they take place.

“I study single-molecule dynamics using a technique called Tethered Particle Motion,” Nir explains. “In TPM, molecules are secured to a substrate at only one end, while the rest of the molecule extends into a fluid-filled vessel, where it has a certain range of free motion. In combination with super resolution microscopy, TPM has given us new insights about DNA dynamics, protein-DNA interactions as well as protein folding – in an environment that closely resembles what happens inside live cells.”

By optimizing TPM methodology, Nir has made it possible, for the first time, to quantify the structural variations that DNA-binding proteins induce.  Working together with Dr. Ronen Berkovich from Ben-Gurion University, he has also devised a biophysical model that successfully describes single-molecule behavior in the presence of laminar flow – the varying flow velocities that occur when a viscous liquid flows through a tube or pipe. In another project, Nir has characterized how chemical compounds – as well as laminar flow dynamics – can be used to stretch and unfold single domains of a polypeptide chain.  

“These advances to TPM technology enhance our ability to characterize and measure what happens during the ligand-receptor interactions that occur at the outer cell membrane, including the invasion of pathogens,” Nir says.

As the newest member of a genetics laboratory headed by Dr. Ting Wu at Harvard, Nir is excited about applying super resolution microscopy to Oligopaints – a fluorescent technology that Wu developed for imaging specific chromosome regions. “With Oligopaints, we can bind specific targets along the genomes of different organisms,” he says. “Not only does this provide a cost-efficient way to study large chunks of the genome, eventually, this might be applied to the imaging of the chromosomal translocations that often lead to cancer and other diseases.”

While not in the lab, Nir joins his family exploring the New England countryside, as well as Boston’s family-friendly cultural attractions. But he has great nostalgia for his days at BINA, and is looking forward to someday setting up his own lab in Israel.

“The faculty members, students, administrators and technicians at BINA are all incredibly nice and capable, and together, they’re capable of producing significant science,” he says. “I have a lot to learn in my new job, but I benefit from the experienced I accrued at BINA, where the facilities are really world-class.”         

(a) Pictorial description of a single particle diffusing in a harmonic potential applied by the DNA. Two different conformations are shown.

(b) P(x, t|x0) for x0 = −650 nm. Dashed red line: for  t = 0.01tau ; solid blue line: for  t = 0.1tau; and dotted black line: for  t = 10tau . Solid green line: the steady-state (Boltzmann) distribution.

Lindner, M., Nir G, Vivante A., Young I. T. and Y. Garini PHYSICAL REVIEW E 87, 022716 (2013)

Originally published by the Bar-Ilan Institute for Nanotechnology and Advanced Materials.