SENS6 Favorites: Breakthrough Protocols to Study AGEs and Combat Viruses by Yale’s David Spiegel and MIT’s Todd Rider

Posted by Iain Inkster on October 25, 2013 | SRF Education

The following is an account of the 2013 SENS6: Reimagine Aging Conference at Queens' College, Cambridge  from SRF intern Brandon Frenz.

The most amazing thing to me about the SENS conferences is their perennial appeal to the non-scientist. It’s interesting to see how many people from unrelated backgrounds come to watch highly technical talks on biochemistry, molecular biology, and regenerative medicine. This is most likely owing to the incredible advances in research being presented at the conference.

One presentation of particular note was given by Associate Professor of Chemistry at Yale Dr. David Spiegel. Dr. Spiegel’s lab studies advanced glycation end products (AGEs). AGEs are by-products of aging that accumulate in the area between cells, called the extracellular matrix (ECM). AGEs have been implicated in a number of age-related diseases, including Alzheimer’s Disease, cardiovascular disease, diabetes, and stroke.

One major hurdle to develop technology to break down AGEs is obtaining sufficient chemically pure quantities for experimentation. During his presentation, Dr. Spiegel explained how his lab is chemically synthesizing AGEs, such as glucosepane, the most abundant AGE found in aged tissue, using thirteen-step synthetic sequence.

 

A new institute focused on protein design is being created at the University of Washington, where I am a biochemistry graduate student. I am particularly excited that synthetically designed AGE-breaker proteins easily could be tested and screen in vivo using Spiegel’s breakthrough technology. I have begun talks with Dr. Spiegel about a potential collaboration and am hopeful that his synthesis protocol has provided the means to develop a method to clear glucosepane from the human body and thus alleviate some age-related diseases.

Another interesting protein-design talk was given by Dr. Todd Rider from MIT’s Lincoln Laboratory. Dr. Rider discussed the development of a new molecule he calls DRACO, which stands for Double-stranded RNA Activated Caspase Oligomerizers. DRACO is a fusion between a double-stranded RNA recognition protein and one of the terminal proteins in initiating apoptosis (programmed cell death). Since long stretches of double-stranded RNA are not typically present in healthy human cells, apoptosis is not triggered. However, when a cell is infected with a virus that generates double-stranded RNA, a DRACO molecule can recognize the foreign RNA and initiate programmed cell death, thereby preventing the virus from spreading. DRACO has already been shown to be effective in various cell lines and has thus far been able to clear a variety of viral infections. DRACO has also been successful in clearing virus from H1N1-positive mice with no observable side effects in the mouse.

One of the remaining challenges to the developing DRACO into a therapeutic is production of the molecule. However, it’s likely this won’t be a major hurdle as the technology to efficiently produce DRACO does exist. In addition to its use as a broad spectrum antiviral treatment, the DRACO technology may also be the key to targeted therapies as well. For example, certain delivery mechanisms, such as protein nanocages,, are being developed that would allow DRACO- targeting to human cells according to surface proteins, such as the HIV receptor CD4. Packaging DRACO inside one of these cages with a CD4 receptor could theoretically provide a targeted therapy for HIV patients by eliminating infected CD4 T-cells while leaving uninfected CD4 cells intact.

These two talks cover just a few examples of the advances that impressed me at SENS6. I also attended the SENS5 Conference, and the rate of progress between SENS Conferences is astounding! I cannot wait to see how the field of regenerative medicine progresses by SENS7 in 2015.

 

For more on 2013 intern Brandon Frenz and his work click here