Chimpanzees share almost 99% of our DNA, yet the way our brain functions, our morphology, our phylogeny, our phenotype, and multiple other factors differ greatly. So how can this be the case? The drivers for these differences lay within the non-coding parts of our DNA – specifically the gene regulatory system. These DNA sequences, instead of coding for a specific protein, tell our genes when to turn on and at what level they should be expressed at what time. Because of these nucleotide differences, genes in the human forebrain have allowed humans to grow smarter, and genes in chimpanzees have allowed them to build a stronger and more resilient immune system.
This summer, I will be working with the Wray lab under Micah, a first-year graduate student at Duke. Even though I will only be working on a small part of the greater project, the end goal of this research project is to investigate evolutionary differences between chimpanzees and humans at the gene regulatory level. More specifically, chimp-human hybrid induced pluripotent tetraploid cells will be cultured to see how DNA from the chimp will interact with DNA from the human, and to see how the gene regulation in the hybrid cells differs from just the human or chimp cells. From this, we can tell what factors affect gene regulation in both species that lead to the different phenotypes observed. This technique can then be further used to look at disease specific differences that could give us insight into how chimpanzees are better adapted for some diseases than humans are, and why.
Even though I hope to see this project to completion eventually, my specific role in the lab this summer will be to work with human induced pluripotent stem cells (hiPSC’s) to differentiate them into neural progenitor cells. To complete this, iPSC’s must first be thawed and cultured in petri dishes. Their stem cell properties must be confirmed using antibody markers that detect specific transcription factors. Next, the stem cells must be differentiated into neural progenitor cells (NPC’s) using a range of different factors such as noggin to direct their gene expression. The identity of these cells must then be confirmed using antibody markers once again for specific transcription factors expressed by human NPC’s. Once these human NPC’s have been produced, multiple tests can be run to gain insight into their cis and trans gene regulatory systems to get a better understanding of how they work in vivo.
I look forward to getting more comfortable with the lab, learning new bench techniques, and making an impact on the greater scope of this project.