The ultimate goal of this work is to get a high-enough resolution structure to where we can start designing drugs. Well, what is a drug? And how do they work?

Check out this video update for the answer!

http://www.youtube.com/watch?v=ycOPz7X3hhU

I sent the video to my good friend Ari, and he had some immediate questions. Instead of just answering them for him, I figured I'd post his quetions and the answer here.

"What about my donation (and other people's...) will help?

When we started this project a few years ago, no one thought it would work. Many people in the past had purified telomerase from Tetrahymena, but no one could get the sample clean enogh to get good electron micrscopy images. You need very little contamination in order to average all the moleucles together, which is how the process works.

So when we started, we worked like mad because the deck was stacked against us. This caused us to really push hard, and not only to finish the project but to do it much faster than anyone had anticipated. This means we do not have enough money in our curent grant to continue at this rate, a rate that needs to happen for us to get the high-res structure.

Your donation will let us continue working like mad now and not have to stop and apply for new money.

"The small part at the end was quickly glossed over. Does it mean my donation will help you get more microscope time? More resources and more staff?"

Yea, it means it will help us get more microscope time and resources. To get more staff would require we raise +$50,000k, which is likely not feasable and also not entirely needed.

To use the microscope costs about $100 per hour. We suspect we'll need to use the microscope for a combined total of about 150 hours. We have about $10k left for EM time and so the $5k pushes us up to the 150 hour mark. If we raise over the $5k, then we can replenish some of the supplies we will have used outside of the EM time. This includes media to grow the critters in, the resin used for purification, and the grids needed to immobilize our sample for EM analysis.

"What is inhibiting your high-resolution modeling and how does extra cash take you over the edge?"

The issue is we are switching from negative stain electron microscopy to cryo electron microscopy. Without divulging too much information, we bascically haven't pefected our purification methods to make the sample amenable to this new technique. When we do—which we will—the only thing needed will be to take images using the Titan Krios (which has a new direct-detection CMOS camera) and carry out the structural calculations.

We reached our goal of $5,000 and beat it! Thanks everyone!

What will we do with money beyond $5,000?

Well, from my experiences nothing in science ever works the first time. So the extra funds will likely be needed to pay for EM time needed to get things to work well. When that happens, if we still have money left we will use it to pay for the materials and supplies needed to grow Tetrahymena and purify telomerase.

Thanks again everyone! We did it!

Best wishes, Edd!

Since we reached our initial goal of $5,000 so quickly, we are going to go for a "push goal" of $10,000. This will allow us to buy a "block" of EM time instead of buying it à la carte, therefore giving us more bang for our buck! Thanks everyone!

http://touch.latimes.com/#section/-1/article/p2p-79371190/

Dear SPARK'ers,

What a wild ride it's been! All the perks have been delivered and I will either personally hand deliver them to you or mail them to you depending upon our spatiotemporal locations.

I come bearing both good news and less good news. The good news is that your donations helped us test a lot of conditions that we would have otherwise had trouble funding. The less good news is that none of these conditions got us a sample that was amenable to obtaining the high-resolution structure. At the end of the day, basic science research is never a failure, so even though these conditions didn't get us that high-resolution structure, we now know which conditions don't work and so can keep screening other conditions! This is actually really important and will help us going forward. 

Since we didn't get a high resolution structure, the perks will be based on the structure we solved last year, which is still pretty cool!

Thanks again for not only funding this project, but for funding science in general!

Best wishes, Edd