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 – bioRxiv Pre-print – 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) bioRxiv. http://biorxiv.org/content/early/2017/06/03/145730
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.
- In Vitro Development of Synthetic Chromatin Proteins That Function in Live Cells. FASEB. Abstract. 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.
Dr. Haynes received an award for SBHSE Outstanding Assistant Professor 2016-2017. Awardees are evaluated based on yearly performance and selected by the Director of the School of Biological and Health Systems Engineering.
Research abstracts from the Haynes lab have been selected to be showcased at the 2017 American Society for Biochemistry and Molecular Biology (ASBMB) annual meeting. ASBMB is a nonprofit scientific and educational organization with over 12,000 members. This year’s meeting will be held at McCormick Place, Chicago, IL April 22 – 26, 2017. Dr. Karmella Haynes will be presenting a talk entitled In Vitro Development of Synthetic Chromatin Proteins That Function in Live Cells on Tuesday April 25 during the Spotlight Session Beyond the Code: Chemistry of Nucleotide and Amino Acid Modifications. For the poster session Protein Engineering and Design, also on April 25th, her doctoral student Stefan Tekel (Biological Design, PhD) will present a poster entitled Using Multivalency to Improve the Function of Synthetic Epigenetic Proteins. Dr. Haynes will also be presenting a poster.
Support: NIH NCI award (K01 CA188164) to K. Haynes, SBHSE Merit Award to S. Tekel
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If you are an undergraduate who is enrolled at ASU and would like to get exposure to lab research-in-action, apply for a position as an Undergraduate Mentee (UGM). Accepted applicants will be partnered with a knowledgeable lab member (mentor) and will shadow their mentor’s research at the bench. UGM’s who are highly engaged may be invited to help analyze data or even set up and run experiments in molecular cloning, cell culture, gene editing, protein engineering, PCR, etc. depending upon the mentor’s current project. UGM’s may participate for as little as two consecutive weeks or as long as one full semester. Read the rest of this entry »