Haynes lab PhD student Alyssa Henning (Biological Design) recently participated in local Comic Con and cultural events in Phoenix. The first event was Phoenix Comic Con on May 25 – 28 where she was invited to talk about real-life science as a panelist. At a Japanese pop culture event called Saboten Con (September 4), Alyssa and the Sun Devil Taiko club (of which she is an officer) won an award for their musical performance.
- 05.24.17. Faller, MB. ASU Now: Sun Devil Life. ASU Experts Bring Real-Life Science to Phoenix Comicon.
- 05.28.17. Reiser, L. AZ Family. ASU Student Looks at Science of Comicon.
Research – bioRxiv Pre-print – The synthetic histone-binding regulator protein PcTF activates interferon genes in breast cancer cells
The synthetic histone-binding regulator protein PcTF activates interferon genes in breast cancer cells
Olney KC, Nyer DB, Wilson Sayres MA, Haynes KA. (2017) bioRxiv. http://www.biorxiv.org/content/early/2017/09/07/186056
Certain types of breast cancer can be difficult to treat because cancer cells in different patients may not be completely identical. Here, we investigated and artificially manipulated the expression states of genes in drug responsive and non-responsive (triple-negative) breast cancer cell lines. Similar to findings from other researchers, we observed that certain groups of genes are commonly or differentially expressed. A large group of genes is epigenetically silenced in breast cancer cells compared to non-cancer cells. We used a synthetic fusion protein called PcTF to physically bridge histone methylation at silenced genes with proteins that drive gene activation. This experiment revealed that nineteen common PcTF-upregulated genes (PUGs) from the interferon pathway as well as other tumor suppressors became activated in all three cell types, including the triple negative cells. PcTF has the potential to act as a powerful therapeutic protein (biologic) that activates multiple anti-cancer genes at once.
ASU Full Circle recently highlighted the emerging Molecular, Tissue, and Cellular Bioengineering (MCTB) community at ASU and the second annual MCTB Symposium, co-chaired by Karmella Haynes.
J. Kullman, 07.27.17, ASU Full Circle: There are more technically precise descriptions of what’s at the core of a growing trend broadening the horizons of biomedical engineering than “the soft, squishy side of bioengineering.” But Karmella Haynes and Kaushal Rege still like the way that sums up what they and about 20 other Arizona State University faculty members are increasingly focusing on in their research and teaching.”
Read more at ASU Full Circle.
Molecular structures guide the engineering of chromatin
Tekel SJ and Haynes KA (2017) Nucleic Acids Res. https://doi.org/10.1093/nar/gkx531
Specialized proteins within the nuclei of human and other eukaryotic cells wrap DNA into a structure called chromatin. For decades, scientists have used biochemistry, genetics, and comparative evolutionary biology to understand the specific interactions and processes that guide the highly-regulated packaging of DNA into chromatin, as well as chromatin features that act to switch gene expression on and off. Basic research has enabled chromatin engineering by rational design for building new tools to further understand chromatin, and for applications such as molecular interventions of cellular disease states. This review highlights key discoveries in chromatin research and engineering efforts that have been supported by this knowledge.
Congratulations to Haynes lab PhD student Rene Daer, who has been invited to give a poster presentation at the 2017 Synthetic Biology: Engineering, Evolution & Design (SEED) conference in Vancouver, Canada May 21-21, 2016. She will present her latest work on manipulating chromatin in human cells to enhance CRISPR efficiency. Rene is a fifth-year graduate student in the Biological Design program.
Research – ACS Synthetic Biology – Tandem histone binding domains enhance the activity of a synthetic chromatin effector
Tandem histone-binding domains enhance the activity of a synthetic chromatin effector
Tekel SJ, Vargas DA, Song L, LaBaer J, Haynes KA. (2017) ACS Synthetic Biol. (just accepted manuscript) https://pubs.acs.org/doi/pdf/10.1021/acssynbio.7b00281
Here, we report the behavior of a re-engineered PcTF, a gene-regulating fusion protein that is designed to activate genes that have been suppressed by chromatin condensation in cancer cells. We added an extra histone-binding domain to create Pc2TF and observed 2- to 4-fold enhancement of target binding and target gene activation. The new design was inspired by natural proteins that also have double-motifs that contribute to target affinity. The specific combination of motifs in Pc2TF does not exist in nature. By using design rules inferred from pre-existing motif patterns, we have improved the performance a novel synthetic chromatin effector. This improved activity advances PcTF towards clinical translation for anti-cancer therapy.
- Pre-print: Tandem Histone-Binding Domains Enhance the Activity of a Synthetic Chromatin Effector. bioRxiv. http://biorxiv.org/content/early/2017/06/03/145730
- Conference Proceeding: In Vitro Development of Synthetic Chromatin Proteins That Function in Live Cells. FASEB. http://www.fasebj.org/content/31/1_Supplement/922.8.short
Dr. Haynes was invited to present her research at the Harvard Medical School Systems Biology Retreat at Seabasco Resort in Phippsburg, Maine. The Systems Biology retreats enable current and former department members to discuss science as a community. Dr. Haynes will present a talk on engineered proteins that bind aberrant marks in cancer cells on Thursday, June 8.