#EB10 Conference Report: Lee Hood – A Systems Biology approach to prion disease
This is a post from the 2010 Experimental Biology meeting in Anaheim, part of the SDBN conference reporting channel.
Leroy Hood probably doesn’t need any introduction here, but for those who don’t know, he’s a leader in using a systems biology to address large, complex medical problems. One such problem is prion disease, a disorder caused by a proteinaceous infectious agent which results in neurodegenerative symptoms as the proteins accumulate in the brain. After decreasing in recent years subsequent to the slaughter of 4.4 million potentially prion-bearing cattle in the UK and establishment of new industry practices, deaths due to prion disease are now as high as they were at their height in 2003.
As prion proteins accumulate and physiology is disturbed, there’s a change in gene expression of over 7400 genes. using 8 mouse strains, Dr. Hood used subtractive biology techniques to narrow the list of relevant genes to 333. Of this number, 2/3 were already known to be involved from previous work. An additional 100+ genes discovered were newly implicated. To study the dynamics of accumulation co-occurring with prion accumulation, Hood developed a massive dataset consisting of transcriptme analysis, histopathological studies, and tissue distribution studied, combining these data with known protein interaction data and clinical signs of disease. This massive analysis identified the accumulation networks and revealed the dynamics of the process as it happens over 20 weeks. In the human, prion disease can gestate for 4 years, so 20 weeks is a reasonable time for a mouse model.
One of the neatest things to come out of this work was a a means of predicting the cell type involved, based on the differential expression of the genes. All the novel prion-associated genes were correctly predicted this way. From within this dataset, they further identified 15 proteins found in the blood which track the clinical course of the disease. Instead of a definitive diagnosis only being possible upon autopsy, now the disease state can be monitored via blood markers, resulting in much easier monitoring of at risk populations and a far safer food supply.
Dr. Hood took a few moments to mention that he’s founded a company, Integrated Diagnostics, which is undertaking some fascinating projects. Among these are creation of a human proteome atlas, which will yield a quantitative assay for every known human protein, and a microfluidic chip platform with some impressive stats. He said the chip would be able to assay 50 proteins in 5 minutes using a volume of 300nL of serum (not whole blood, I assume) at attomolar sensitivities. With that level of sensitivity, they’re well within clinically significant ranges for most proteins.
To do this, they invented a novel protein capture technique that used a combination of low-affinity 6mers and click chemistry to create highly stable chips with antibody-like specificity. he cited 5 years until their availability.
In 10 years, he expects genome sequencing to be routinely done as part of medical practice, costing no more than a couple hundred dollars (as the inventer of automated DNA sequencing, I’d believe him). What this would allow, for example, is capturing of an individuals MHC locus during allergy testing and identification of specific auto-antibodies.