proteins

Why have we not found the cure for cancer yet? Neil deGrasse Tyson, Chuck Nice, and Gary O’Reilly explore paradigm shifts in cancer treatment, molecular biology, and a promising new cancer drug AOH1996 with City of Hope cancer researcher Dr. Linda Malkas. 

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Photo Credit: Dr. Cecil Fox (Photographer), Public domain, via Wikimedia Commons

Welcome to the second episode of Bio Eats World, a brand new podcast all about how biology is technology. Bio is breaking out of the lab and clinic and into our daily lives -- on the verge of revolutionizing our world in ways we are only just beginning to imagine.

Many diseases are caused by proteins that have gone haywire in some fashion. There could be too much of the protein, it could be mutated, or it could be present in the wrong place or time. So how do you get rid of these problematic proteins? In this episode of Journal Club (now on Bio Eats World), Stanford professor Carolyn Bertozzi and host Lauren Richardson discuss the article “Lysosome-targeting chimaeras for degradation of extracellular proteins” by Steven Banik, Kayvon Pedram, Simon Wisnovsky, Green Ahn, Nicholas Riley, and Carolyn Bertozzi, published in Nature (2020).

Dr. Bertozzi and  her lab developed a class of drugs — or modality — that tosses the disease-related proteins into the cellular trash can. While there are other drugs that work through targeted protein degradation, these drugs called LYTACs are able to attack a set of critical proteins, some of which have never been touched by any kind of drug before. The conversation covers how they engineered these new drugs, their benefits, and how they can be further optimized and specialized in the future.

Proteins are molecular machines that must first assemble themselves to function. But how does a protein, which is produced as a linear string of amino acids, assume the complex three-dimensional structure needed to carry out its job? 

That's where Folding at Home comes in. Folding at Home is a sophisticated computer program that simulates the way atoms push and pull on each other, applied to the problem of protein dynamics, aka "folding". These simulations help researchers understand protein function and to design drugs and antibodies to target them. Folding at Home is currently studying key proteins from the virus that causes COVID-19 to help therapeutic development. 

Given the extreme complexity of these simulations, they require an astronomical amount of compute power. Folding at Hold solves this problem with a distributed computing framework: it breaks up the calculations in the smaller pieces that can be run on independent computers. Users of Folding at Home - millions of them today - donate the spare compute power on their PCs to help run these simulations. This aggregate compute power represents the largest super computer in the world: currently 2.4 exaFLOPS!

Folding at Home was launched 20 years ago this summer in the lab of Vijay Pande at Stanford. In this episode, Vijay (now a general partner at a16z) is joined by his former student and current director of Folding at Home, Greg Bowman, an associate professor at Washington University in St. Louis, and Lauren Richardson. We discuss the origins of the Folding at Home project along with its connection to SETI@Home and Napster; also the scientific and technical advances needed to solve the complex protein folding and distributed computing problems; and importantly what does understanding protein dynamics actually achieve?