What is Death?
Many research efforts have been devoted to studying the genetic, epigenetic and environmental bases of longevity, shortevity, and the essential components of life. Little attention, however, has been given to biological processes following death.
In this study, we carry out a longitudinal genome-wide investigation of the processes that follow death. Using humanized mice as a model system, we employ high-throughput genomic techniques and systems biological methodologies to identify genes that are differentially regulated following death. Comparison between pre- and post-mortem gene expression patterns, using time-course RNA-seq data, reveal the essential genetic components responsible for a healthy death. To assess the biological relevance of the identified genes, nonnegative matrix factorization (NMF) is used to reconstruct the genetic network architecture responsible for the death phenotype. The identification in this study of a hierarchically organized gene regulatory network led to the hypothesis that mutations in specific master regulatory genes should be capable of inhibiting death. This hypothesis is corroborated by complementation experiments that rescue, and thus initiate, the death phenotype. We also show that the NULL death evasive mutant allele, dem-/-, is lethal. These experiments are performed on numerous tissue types ranging from brain to toe nail.
Next, using chemical and biological assays we plan to investigate all 21 genes found spread over 10 chromosomes (including the X-chromosome) having a total of 74 dem family allelic and splice variants that affect the death phenotype (oddly enough, all genes share one transcript in common; that which contains no exons). Then, we will identify parental-origin-specific genome-wide SNPs, CNVs, whole-genome siRNA, dsRNAi, and all other epigenetic modifications to elucidate the differential contribution of the parents' sex to the death of their offspring.
Incidentally, our study provides the first rigorous whole-genome measurements of tissue specific RNA degradation rates. These can be used to address numerous biological and biomedical questions as they pertain to both living and dead organisms.
Figure 1: Exemplified preliminary data.
To our disbelief we have yet to secure funding for this improbable research. Information about funding opportunities, donations, and volunteers of any species (pre- or post-mortem) are most welcome.