The research partnership with the Utah State Office of the Medical Examiner has given the team more than DNA samples. In a recently initiated project through additional IRB approval, the team is collecting skin biopsies from suicide victims and post-mortem brain tissue with next-of-kin consent. As with the DNA, all tissue samples are linked to the database resources in the UPDB, but then are completely de-identified for subsequent research.
Use of Brain Tissue
Using brain tissue, it is possible to look for expression of the genes identified in the DNA samples. Gene expression analyses can conversely be used to further guide the DNA analyses, looking at specific genes or gene pathways that show abnormal expression. Given the heterogeneity of suicide, it is crucial to look at the right sample subset in the post-mortem tissue.
As brain collection from suicide victims is a slow process, and the research team will have to bide their time, banking tissue until they can match tissue with DNA having a specific genetic profile. The value of the post-mortem brain tissue doesn’t end here. Synaptic dysfunction is implicated in suicide, and team members have the expertise to study synaptic characteristics in the brain from the suicide cases might further guide the search for genes involved in the increased risk of suicide. As with the gene expression data, this will be an important complement in the search of genetic variation, governing which genes to focus on.
Brain tissue will also be stored anonymously at one of the NIH-funded brain banks. These are part of the Neurobiobank, a network of brain banks to provide a national resource for the study of disorders that affect the brain. The National Institutes of Health coordinate these research efforts and ensure that studies meet the highest standards of research, in addition to protecting the privacy of donors. The Utah Suicide Genetics Project is proud to be a contributor to this network.
Learn more about the Neurobiobank.
Stem Cell Technology
With the recent advances in stem cell technology, cells from skin tissue can now be converted to stem cells, called induced pluripotent stem cells or iPSCs. The technique, while still technically difficult and costly, is a huge step forward in medical science. Not only is it now possible to grow neuronal cells from iPSCs derived from fibroblasts, but employing iPSC techniques might also answer questions on an individual level.
As the study progresses, the team plans to use fibroblasts from subsets of suicide cases with validated, high-risk gene mutations that have persisted through rigorous statistical and molecular tests, to produce neuronal cell cultures from fibroblasts. This approach, together with the post-mortem brain tissue, will open up a whole new avenue for functional studies. Having living neurons in culture, derived from individual suicide victims, allows studying the functional consequences of an aberrant gene.
Also on the agenda are re-expression experiments: reversing a deficiency to study the functional outcomes. On top of that, neuronal cell cultures can eventually also be used to test for potential pharmacological therapies, studying the effects of drugs on the cells.