A protein in a box

Exactly one year ago today I defended my doctoral thesis in Delft. Fast-forward one year, and I find myself writing these words in the California sun. How different life has become! Having embarked on an exciting new project, I am now challenged to think about a whole new universe of fascinating problems. Yet I do enjoy looking back every now and then to remember the good times of grad school. The good times of a protein in a box.


What is life? At the very least it is a concept that we humans find surprisingly difficult to define. Though generally wet and dynamic1, arguments about what defines life inevitably involve terms like ‘reproduction’, ‘growth’, and ‘adaptation’ – matters very common to cells and viruses alike, yet whether the latter belong to the category of living things is a matter of ongoing debate. For the purpose of this thesis (as well as for my own understanding), I adopt a less materialistic and more conceptual definition of life:

Life is a process brought forward by the self-organization of molecules, a process that seemingly violates the second law of thermodynamics2 as it increasingly acquires and maintains information over timescales that vastly exceed the lifetime of the molecules holding this information.

In this manner the distinction between a virus and a cell becomes rather meaningless: viruses are just as much part of the process that we know as ‘life’ as a homo sapiens like you or me is.3 In addition, it allows me to conveniently classify my thesis work as “an effort to gain better understanding of the molecular processes and building blocks of life”. Though this classification is rather broad – as myriads of doctoral theses written over the past century or so belong to this category – my thesis belongs to a relatively small and novel subcategory of the ‘gaining insight into the building blocks of life’ class by making use of two concepts: single-molecule and bottom-up approach.

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Death by fungicide

talk about having an off day
Talk about having an off day.

Stumble upon Sunday. This reminded me of a fascinatingly morbid BBC (earth?) series. A fungus that takes over control of an insect brain, directs it towards an area optimally humid for fungal growth, lets the zombified critter bite down into a leaf to anchor it in place, then finally kills and devours it. How on earth does this work? How does something like this evolve? In any case: it makes for great pictures, as Alex Wild shows.

That time when there was too much magic in your mushroom

Tus fuss (1)

 

The main actors.

My Tus paper in the news, those interested can start reading up. Again, more to follow

 

Today’s headlines

Is it a bird? Is it a plane? No: It’s my project on the cover of Nature Chemical Biology!

Tussle stories.

More will follow soon, for the time being I’ll quote the Journal:

“A single-molecule approach using magnetic tweezers shows that DNA strand separation alone can trigger a lock at Tus–Ter sites where oppositely moving replisomes on circular bacterial chromosomes must avoid crashing. The results support a ‘mousetrap’ model in which replication-related proteins are not necessary and strand separation is followed by an interaction between Tus and C6 of the Ter site that sets up a hierarchy of interactions to allow the Tus–Ter complex to progressively strengthen. Cover art by Erin Dewalt, based on an image provided by TU Delft/Tremani.”

Supporting conversations

During a recent conversation with a technician, let’s call him ‘Cherry Maker’ (CM, not to be confused with cherry picker), I wanted to know what being support staff meant to him. “Assimilation.” he answered, and after seeing my puzzled face, he added: “It’s becoming what you always dreaded as a researcher.” “Well”, I said, “isn’t that a bit dramatic?” CM: “No! I find it quite funny. When I was a young grad student a long time ago, I found the sight of a technician going home at 5, irrespective of the status of the experiment, horrifying. Same when a technician’s interest in a paper did not go beyond his/her own contribution.”

The distorted views of academia. This image is really spot on (@biomatushik – http://sotak.info/sci.jpg)

“Now” he said with an ironic smile, “I can just feel those looks from grad students as soon as I leave for home at around 5! Look Bojk,” CM said in his usual tongue-in-cheek manner, “you PhDs like to think it’s all about you and your research, but as a technician you have come to realize that hierarchy and continuity come first, then comes a whole lot of nothing and other stuff, and then come the PhDs…” Me: “So where’s the assimilation part in this and why is this funny?” CM: “Because I realize now that every researcher-turned-support unavoidably assimilates towards this other way of thinking, irrespective of the initial world view. It’s nurture pur sang!”

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Scientific lubricant

Remember me writing about how stressful life as a last-year grad student was? How many of us walk around sleep deprived, nervous and pale in the face? Forget about all that, life as a final year grad student rocks!

Climbing peaks in Aspen: single-molecule biophysicists in the Rockies. (Steve Block’s Single-Molecule Biophysics meeting, Aspen, CO)

Let me tell you why. For the better part of 3 years you have spent an innumerable amount of time trying to figure out why you are the right (wo)man for the job, messing up, experimenting with flexible working hours, procrastinating, doing useful and less useful experiments, isolating yourself from family/friends/daylight, feeling insecure about your future and ignoring important e-mails from department secretaries. You may even have contemplated quitting, or at least pondered what life would be like as a diving instructor, mountaineering guide or Buddhist monk. But now all of a sudden the mist that clouded you so hopelessly has cleared up as if being burnt away by the morning sun: now you have a story to tell. This means it’s conference time!

And some more in the Alps (Kavli institute Delft retreat, Courchevel, France). 

Those outside academia might now be wondering whether the clearing of the above-mentioned mist also took away my last bit of sanity, but those in science know better. For scientists may not earn six-figure salaries, they will not find themselves surrounded by groupies on a regular basis, and they may have to spend days on end measuring in a basement, but I have to say: they sure know how to treat themselves to a proper intellectual retreat.

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Het ei is gelegd: een polymerasepaper in 4 stappen

Zo, het heeft even geduurd, maar eindelijk is het dan zover: het ei is gelegd. In de vorm van een artikel, dat dan weer wel. Leefde ik aan het eind van mijn eerste jaar (anno 2012) nog in de waan dat het een kwestie van weken zou zijn voor publicatie, weet ik nu dus wel beter. Het p2 onderzoek waar ik een flinke bijdrage aan heb geleverd – waardoor het werk een stevige positie in mijn toekomstige proefschrift heeft gekregen – heeft van begin tot eind zo’n 7 jaar in beslag genomen.* Karakteriseren met termen als ‘uitputtingsslag’ of ‘marathon’ zou derhalve een understatement zijn. Hoewel het gros van de data in 2012 al gemeten is, heeft het verhaal in de jaren daarna met name wat dataverwerking en -analyse betreft nog een enorme ontwikkeling doorgemaakt. Wat we nu presenteren is een compleet verhaal geworden dat zowel op experimenteel als op theoretisch vlak vernieuwend is. Dit zeg ik niet alleen omdat ik bevooroordeeld ben, om 4 redenen brengt dit werk wat nieuwe dingen naar voren, begin hier met lezen!

NB Is deze tak van sport helemaal nieuw? Lees dan hier waarom we überhaubt aan een enkel molecuul zouden willen meten, hier een inleiding over de magnetische pincet (magnetic tweezers) en hier mijn vorige verslag over dit project. Continue reading “Het ei is gelegd: een polymerasepaper in 4 stappen”