Friday, June 29, 2018

Thinking, working, racing and sweating -- Velosano 5: 100% for the cure.

I owe a lot of updates from the lab, but first let me advertise a bit for a charity bike ride I'm doing in next month.

Like last year, I am riding in the Velosano cancer charity bike ride. I will be riding 200 miles over two days in support of important, innovative research done here in Cleveland under the auspices of the Cleveland Clinic and the Case Comprehensive Cancer Center.  Last year was my first year riding, and thanks to you, I raised over $4,000 (over $4 MILLION was raised overall). I started alone (this is a LONG ride to do alone), but eventually was adopted by a 'wolf pack' of riders who I had never met. This group of riders became like a little family over the next two days, and included founding members of the ride.


What I didn't know at the time was the my lab would end up being directly supported, to the tune of $100,000 by this ride. This is particularly important, as we are a young lab, and do thing quite differently than many, and this seed grant has allowed us to think completely outside the box -- and to pursue a project that would have little chance at standard funding methods.  I'd like to tell you a little about it.

First off, I think it's important to realize that I see cancer research almost entirely differently than most do.  I am not interested in new drug development (this takes decades, and BILLIONS of dollars) because we already have excellent drugs... we just don't know how to use them in the face of a changing, evolving foe.  Cancer, like all living entities, responds dynamically to external stresses... by EVOLVING. Therefore, the focus of our lab (which you can find out more about here) is the purposeful, direct study of the evolutionary process.  We are not interested in any one of the uncountable ways cancer evolves resistance to drugs (mutations) but instead on the process by which these solutions are chosen. We study this in a number of ways, typically with mathematics.

Example results of ODEs describing the growth of a well-mixed population limited by nutrients and killed by drugs.

Recently, however, we have begun to start thinking about how to design experimental systems that give us the ability to constantly monitor the genomic changes in evolving populations of cancer cells -- the idea being if we can monitor these changes in real time (not just after months of treatment), we can learn the patterns in more detail. We are seeking to know our enemy's ways, not just stop any individual plan. To do this, we have had to rethink how experimental systems work, and to design one of our own, which we call EVE (the EVolutionary biorEactor). EVE will be a robotic system consisting of state of the art sensors, computer programs we had to write ourselves, microcontrollers, pumps, and an interface between the biology itself, and this robotic system. This requires many scientists, from many disciplines to come together -- making funding from tradition, focused, funding boards almost impossible. We are basing this system on a 'morbidostat' that was published previously, and also are using some open source parts from the eVOLVER project - but the application to cancer is brand new, and making the jump from bugs/yeast to cancer carries a lot of difficult bits.

Schematic of the board connecting the micro-controller to sensors and pumps.

A basic schematic of the morbidostat system to be extended

With flexible funding like that raised in this event, however, the funding board can take a risk... and while I'm not suggesting that this device will sort out all our problems, history tells us that breakthroughs come from the fiery interface between disciplines, which is where my lab sits.  There are some cool schematics and diagrams you can see describing this project (and others) in our lab on our research in progress page here.

We have also just recently gotten the baseline device working, and can now proudly show off a gorgeous logistic growth curve ...  next steps are to start killing the bugs.  

holy moly - it's logistic growth!!!  (optical density vs. time E. coli growth in media, no antibiotics, well done Nikhil and team)

While we're still behind the groups that pioneered these systems, we are learning fast, and will soon start evolving cancer cells, and testing drug combinations in earnest to see if we can steer evolution, optimize the timing of therapy, and test how repeatable evolution really is, and how this maps to secondary drug sensitivities.

If you gave to my ride last year, THANK YOU, and please consider continuing your support of this important process.  If you are a first time donor, THANK YOU for considering, and know that every dollar counts.

These grants help support the equipment and salaries of the hard working folks who make this research happen. Many folks in the lab have touched this project, but Nikhil, Julia and Erin have been the driving forces of late - and so we went to a Velosano launch party last night to show off the research. Nikhil even brought along some props to show off to interested passers-by, in this case Kara - part of my wolf pack!

tl;dr: I'm hoping to get to $5,000 for my ride this year - please consider helping me.  If you can't donate, please consider sharing this post, or the donation link (below), with your social network to help expand the reach.  The fight against cancer is one we are all touched by. 

If you are in the Cleveland area, you could also consider joining our team, or volunteering - every rider, every dollar and every volunteer help the cause.

To donate to my ride, and to support cutting edge research like this, please follow this link, and press the green DONATE button.

Monday, April 2, 2018

Endogenous miRNA sponges mediate the generation of oscillatory dynamics for a non-coding RNA network

Hello all!  It's been a grant-writing heavy early spring without much new science coming out.  Stay tuned for some news on revisions we've submitted... hopefully good.

Just a quick note, as +Andrew Dhawan has covered most of it. Just wanted to share some excitement about a new preprint from our group which you can find here:

 A full 'Story behind the preprint' to be found on Andrew's blog: Tabula Rasa

But to whet you interest, here is a little tweet thread I made, and you can see some of the conversation - even pointing us to some good references we missed, thanks Marc!

Monday, January 15, 2018

New lab website, a Reddit experience and the Strogatz effect...

Now that things are starting to settle down after my move, writing up thesis, doing oral boards, setting up new practice: most of the BIG things are done. The nice part about this is that I have been able to start thinking about the LITTLE things - little things which often matter a lot, but necessarily fall lower on the hierarchy of needs than the BIG things.

On this list has always been to set up a lab web site, which is finally done.  Thanks in no small part to a post-doc who's working with me, Inom Mirzaev, and Mike Baym (a twitter buddy who's html code I stole to use as boilerplate). Anywho, it's live and you can see it here - I'd love feedback... just leave in comments or email me...

We did a bunch of (what I think are) cool things, one of which was to embed an altmetric badge on the site next to each publication. This was SUPER easy, and looks pretty nice, I think.  You can find info on how to do it here (I don't speak html, and it was really easy), and you get this nice effect:

Which is the article I wrote the 'story behind the paper' for the last post.  And, holy crap that is by far my highest Altmetric score (the Strogatz effect - in addition to it being a lasting piece of high quality work)... and it brings me to the final part of the title, my first Reddit experience.  eLife (great journal, great publishing experience... more on that later) has a running relationship with Reddit, and they asked Steve to do an AMA (an 'Ask Me Anything') about this paper. 

Murray (the dog) didn't show up, but we did have a spirited discussion with a bunch of folks asking questions about the paper, and about life in general. It was my first time on Reddit in any capacity, so I just chimed in when I thought it was appropriate, and I think a good time was had by all. Not sure how it works, but I might try to host an AMA about #mathonco or #mathevo next time we have a paper out. Let's see if +Artem Kaznatcheev or +Dan Nichol 's papers are first (ooh - or actually I'd bet Nara's is...)