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Anthony Ciancone's Genomics First Assignment Page



'Undead' genes come alive days after life ends

Click here to view the article. Alternatively, click here to view the original paper's source.

1) What was the research project?
The article I read for my first assignment was entitled "'Undead' genes come alive days after life ends" and was written by Mitch Leslie. According to the article, Dr. Peter Noble of the University of Washington, Seattle, and his colleagues were testing new methods for calibrating gene activity measurements on recently deceased species, specifically on mice and zebrafish. They were also observing any notable changes in gene activity in these deceased animals up to four days postmortem.

2) Were they testing a hypothesis or doing discovery science?
Noble and his colleagues were primarily intrigued to see how well their methods worked on these deceased animals, as Noble stated: "Itís an experiment of curiosity to see what happens when you die." However, Noble and his team were also further testing how well their novel analytic technique worked. They did not have a specific hypothesis to test but rather had an interest in seeing how they could apply their new methodology.

3) What genomic technology was used in the project?
Nobel and his colleagues claimed to be using new methods for calibrating gene activity measurements, but did not delve into much further detail. Previous experiments utilizing the blood of human cadavers had identified a handful of genes but Noble and colleagues analyzed over 1000 using their novel methodology. They tracked any genetic changes over a two day period for the mice and a four day period for the zebrafish. The discoveries included many genes that not only increased activity up to 24 hours after death but even some that remained active for up to four days, as shown in Figure 1.

Figure
Figure 1. mRNA activity vs. time passed in hours. According to the study, this was looking at genes which were specifically abundant in mRNA production
postmortem. The y-axis is an arbitrary unit comparison to standard or expected mRNA production from these genes in living controls. The x-axis is simply how
much time passed from when they started recording the data, not from when the organism died; however, these two times were relatively close when compared to
the overall time frame.

Although many of the genes identified were related to inflammatory and immune responses, the surprising discovery was that many 'developmental genes' turned on after death. These 'developmental genes' were thought to be used to help sculpt the embryo and not used again after birth. Not only that but many genes known to cause cancer saw a similar increase in activity.

While the researchers grappled over theories as to the purpose of such gene expression, some potential uses proved immediately clearer. According to the researchers, the cancerous genes' increased potency could explain why organs received from deceased donors predispose the receiver to getting cancer. In a subsequent paper, Noble claims that observing these genes could provide forensics teams with the ability to pin point time of death more accurately. Further uses may not be as apparent but further time and research may elucidate some of these facets.

4) What was the take home message?
The take home message from this article is that we can learn a lot about genes from studying not only living organisms but also deceased ones. However, many questions remain as to what this research really means. Why are embryonic genes activated after death? Could these findings lead to better donor matches? Is this study translatable to humans, or is it restricted by its dependence on mice and zebrafish? It appears that more questions remain than this study provides answers for.

5) What is your evaluation of the project?
My evaluation of this project is that this is a very intriguing finding and other research should be done to not only confirm the findings but also assess its utilities, especially when applied to humans. I would be more interested in learning about the specific genomic techniques utilized by Nobel and colleagues. How exactly do they differ when compared to contemporary methods? Why would these methods be best suited for this project? Another question I had was why Noble and his team did not simply study cadavers to immediately ascertain applications for humans. They draw many comparisons but do not address this shortcoming. Overall, however, this study was very well-done and did a terrific job at assessing an array of genes and their activities over a specific time frame.


References:

Leslie, Mitch. "'Undead' Genes Come Alive Days after Life Ends." Science | AAAS. Science, 06 July 2016. Web. 02 Feb. 2017.

Pozhitkov, Alexander E., Rafik Neme, Tomislav Domazet-Loso, Brian Leroux, Shivani Soni, Diethard Tautz, and Peter Anthony Noble. "Thanatotranscriptome: Genes Actively Expressed after Organismal Death." Thanatotranscriptome: Genes Actively Expressed after Organismal Death | BioRxiv. BioRxiv Beta, 11 June 2016. Web. 02 Feb. 2017.


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