Archive for November, 2007

Anti-aging drugs, metabolism, and disease

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Since today is my birthday I find myself thinking about aging. I went back and listened to one of the first FIB podcasts. It features Leonard Guarente, who helped start Elixir pharmaceuticals, a company specifically targeting aging and metabolic disease. Here’s a link to the mp3.

Is aging just a disease? Metabolism and aging appear to be very tightly coupled. Even more interesting is how calorie restriction (starvation) has a direct impact on reproduction and lifespan. Dr. Leonard Guarente identified the SIR2 gene 6 or 7 years ago. Sirtuin enzymes (pictured above) are NAD-dependent and activated under special conditions like starvation. The biochemistry suggests that therapies could be possible. Knockout the SIRT1 gene in mice and the quality of life is greatly decreased. Starve any organism from yeast to chimps and they live longer by activating specific pathways. There’s 7 genes in mammals so there’s obviously much left to be understood. Trying to inhibit specific enzymes is pretty common, but targeting pathways and complex signaling in cellular metabolism can be tricky. The signals exist in nature. The technology developed in systems biology and metabolomics could really help answer some important questions in the next 10 years or so.

Avalon pharmaceuticals has a technology for generating pathway signatures, so rather than screening compounds against a single target they claim to be able to target entire pathways. They also have an advanced candidate for solid tumor cancers that’s an IMPDH inhibitor. IMPDH is another NAD-dependent enzyme that I have done a small amount of work on.

WiiMD: Bowling on Big Ben

SC07

SC07 is in full swing in Reno. I promised some details about the PSC booth, more specifically the Wiimote controlled Molecular Dynamics demo. Some credit for this idea should go to Adam Marko, who is now a graduate student at UCSF joining the lab of Andrei Sali.

The real selling point of the Nintendo Wii video game console has been the Wiimote. For those who haven’t experienced one, the Wii Remote is very different from a typical video game controller. It has a built in accelerometer, motion sensing, and optical sensing. It communicates over bluetooth, and best of all it only costs around $50 US. These features work to enrich video games through unique human-computer interaction. The sports games that come bundled with the Wii demonstrate how previously mundane gameplay such as bowling, baseball, and tennis can be a blast with clever interaction design.

In the context of biotech, haptic interfaces could really have a big impact in how biologists, life scientists, and medical profesionals interact with computers and devices. The computer geek in me wants to believe that a keyboard and mouse is the one true way to use a computer but the success of video games consoles, Tablet PC’s, and iPhones are changing the face of computing. Imagine biosimulations which are no longer just scripts, plots, and post-process rendering but rather augmented reality. Where a scientist can use virtual instruments and interact with their simulations in real time.

Before I get ahead of myself, let me explain the demonstration you can see at the PSC booth if you’re attending SC07. It is quite simple to use a Wiimote to replace your mouse on a standard PC. Several months ago we played around with Wiimotes on our workstations, manipulating protein structures in VMD and CHIMERA which are both excellent molecular graphics and modeling programs. In this case the Wiimote just acts as a mouse, and doesn’t really offer much advantage, especially for someone who uses VMD with a mouse and keyboard. Pretty cool, but not very practical for me personally. So the Wii Remotes were left in the drawer until discussion about demos for SC07 arose. That’s when some other PSC heads got involved and the idea blossomed.

VMD is a cool program to use with a Wiimote, but a moving a single protein structure isn’t very interesting. Let’s do a NAMD simulation instead. Better yet, let’s use IMD to have an interactive NAMD simulation. And while we’re at it, let’s run it live on Big Ben (PSC’s 4,000+ processor Cray XT3). After all, Supercomputing is our middlename. The “WiiMD” demo is live at SC07 thanks to key efforts by Nathan Stone, Shawn Brown, and student Jordan Soyke. Unfortunately I could not be there to see the final result, but some work was done with PDIO, a middleware that routes data straight from the nodes of the XT3 to a remote location in real-time. There was also a rewrite of the Wiimote input driver, which Jordan talks about briefly in his blog.

Stop by the PSC booth if you get a chance. I hope to have pictures or video of the demo up sometime soon.

PSC Live! at SC07
WiiMD, interactive molecular dynamics with a wiimote?

And my two favorite blogs have noticed!
scalability.org - Coolest demo I saw today
BBGM - Finally found a reason to buy a Nintendo Wii