Biocurious is a weblog about biology, quantified.

Piled higher. and Deeper.

by PhilipJ on 13 May 2007

My Master’s thesis is being bound somewhere (or so I’m told), and my days left at Simon Fraser University are winding down. For the next month I’ll continue on the optical tweezers I helped build, extending various short biomolecules to figure out their elastic properties. Leading up to more exciting work, I’m trying to reliably tether and pull on extremely short pieces of double stranded DNA, which is challenging from a technically standpoint. I’m not sure how much it helps, but I’ve started using smaller beads (1 μm), but even then it is very difficult to reliably tether and measure single molecules between the beads. Too many DNA molecules makes the beads stick hopelessly tightly together, and too few means I’m sitting around all day waiting for the unlikely tethering event to occur. But in either case, it’s nowhere near as unpleasant as shitting yourself for science.

But I am looking forward to a change, scientifically. Single-molecule biophysics has only in the past few years become a mature area that is answering really interesting and novel questions, but, for whatever reasons, it isn’t for me.

I hadn’t mentioned at the time, but my trip to Toronto was really two-fold: the Chemical Biophysics Symposium was a great small conference, but I was also there to visit labs as a prospective Ph.D. student — in the chemistry department!*

All of the labs I visited were doing interesting things, but you can only choose one. Instead of looking at the force-mediated dynamics of biomolecules as I have been for the past couple of years, I’m switching gears to look at (and maybe control) the dynamics of proteins on ultrafast timescales. The Miller lab is an ideal place to do this, where they’ve recently been optically controlling isomerisation of retinal in the protein bacteriorhodopsin with intensity- and phase-shaped light. From a recent paper (subscription required to read the full article):

By modulating the phases and amplitudes of the spectral components in the photoexcitation pulse, we showed that the absolute quantity of 13-cis retinal formed upon excitation can be enhanced or suppressed by ±20% of the yield observed using a short transform-limited pulse having the same actinic energy. The shaped pulses were shown to be phase-sensitive at intensities too low to access different higher electronic states, and so these pulses apparently steer the isomerization through constructive and destructive interference effects, a mechanism supported by observed signatures of vibrational coherence. These results show that the wave properties of matter can be observed and even manipulated in a system as large and complex as a protein.

The details of my project haven’t been worked out, but it is bound to be extremely cool.

* It’s a good thing we recently changed the tagline from “physicists exploring an interest in biology”!

  1. Kevin    4114 days ago    #

    That’s amazing. I did my Ph. D in the Miller group (graduated in ’03)! In fact, so did my wife after a masters at SFU. Dwayne is among the very best scientists you will ever meet—I was infinitely fortunate to work with him. Most important is his ability to identify and attack the most important and fundamental questions, while developing technological breakthroughs to answer otherwise unanswerable questions.

    It is interesting to note that in 1996, I started grad school thinking I was going to control bacteriorhodopsin photoisomerization with shaped pulses. That idea was slightly ahead of its time, and I switched to another hugely challenging project to study liquid dynamics. It is fantastic to see that Dwayne was ultimately successful, and many of the technical developments needed to carry out those experiments were pioneered by him specifically for that purpose. He has amazing scientific vision, and a long-term commitment to getting every ounce of truth out of a measurement. I would say that basically every aspect of my current approach to my own research group and science in general was shaped by the unique and wonderful mentorship Dwayne gave me.

    You should have a blast!


  2. PhilipJ    4114 days ago    #

    Hi Kevin,

    I really love hearing such encouraging words. Starting over again at a new lab and field is a bit intimidating, but hearing this really helps reassure me that my decision is sound. The environment really did seem top notch when I visited, but more data always helps.

    If you’re back in Toronto for a CBP symposium in the future, let me know!

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