Research – bioRxiv Pre-print – Enhancing Cas9 Activity in Heterochromatin

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Enhancing Cas9 Activity in Heterochromatin
Daer R, Barrett C, Haynes KA. (2017) bioRxiv.

CRISPR is a powerful and popular tool for editing DNA in living cells. Scientists are becoming more interested in using CRISPR to correct mistakes in DNA that lead to diseases, to artificially generate mutations to research the origins of diseases, and for other important applications. However, CRISPR originated in bacteria and has probably not evolved to function very well in genomes that are packed in configurations (open and closed chromatin) as complex as those found in human cells. In a recent report (Daer et al. 2017), we demonstrated that CRISPR activity was inhibited at a DNA sequence that became artificially condensed into closed chromatin. Our new study shows that targeted re-opening of closed chromatin leads to enhanced CRISPR activity in the same region. The epigenetic drug we tested (UNC1999) was not sufficient to generate a transcriptionally active or CRISPR-accessible state. In contrast, strong direct activation with a DNA-binding p65 protein did enhance CRISPR accessibility. Importantly, we learned that a recovery period (following treatment with p65) is needed to generate the CRISPR-accessible state.


Congratulations to the ASU 2017 iGEM Team

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The 2017 ASU International Genetically Engineered Machines Competition (iGEM) team brought home a Gold medal and two nominations for competitive prizes. The team presented their project “EVR QST: Engineering Variable Regulators for a Quorum Sensing Toolbox” to a panel of judges (academic, policy, and industry professionals) and an international audience. The 2017 iGEM Giant Jamboree took place in Boston, MA at the Hynes Convention Center on November 9 – 13, 2017. Read the rest of this entry »

Dr. Haynes to Present CRISPR Research at SERMACS in North Carolina

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Dr. Haynes has been invited to present her group’s latest research on the efficacy of CRISPR editing of human DNA at the 2017 Southeastern Regional Meeting of the ACS (SERMACS) Synthetic Biology Symposium on Thursday, November 9, 2017 in Charlotte, NC. Using a synthetic, regulatable DNA packing system Dr. Haynes and her team, including lead grad student Rene Daer, discovered that chromatin structures similar to those found at stem cell genes can block CRISPR from access to DNA (Daer et al 2017 ACS Synthetic Biology; featured on PRI Science Friday). This can pose a problem for gene therapy and tissue engineering. In her talk “Manipulation of chromatin to enhance CRISPR activity” Dr. Haynes will present a review of these findings as well as recent results from experiments to counteract chromatin and enhance CRISPR activity. The NIH NCI Geographic Management of Cancer Health Disparities Program (GMaP) provided an award to support Dr. Haynes’ travel.

The Haynes lab receives ASU-Illumina Mini Grant

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Dr. Haynes has been awarded a mini-grant for RNA-seq analysis of cancer cells that have been treated with a synthetic protein that her group has engineered. Stefan Tekel, a PhD student in the Biological Design Program, is credited for the work that lies at the heart of this project. He engineered a cell-penetrating version of the protein that can be produced at low cost in E. coli bacteria, purified, and then added (as a solution) directly to cancer cells. The group aims to use the RNA-seq to apply for a major grant in the near future.

Dr. Haynes invited to speak at UC Irvine

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Dr. Haynes has been invited to the University of California Irvine to present a talk entitled “In Vitro Development of Chromatin-based Biologics for Breast Cancer” for the UCI Biomedical Engineering Lecture Series on Friday, October 20, 2017 in the McDonnell Douglas Engineering Auditorium (MDEA).

Dr. Haynes invited to help chart paths of synthetic biology in Paris

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CRI_ParisDr. Haynes has been invited by scientists at the Center for Research and Interdisciplinarity (CRI) to speak at “Charting Future Paths of Open Synthetic Biology” in Paris, France. She will present a talk entitled “Engineering the human genome as chromatin” and participate in advising a strategy (white paper) for the recruitment and support of research fellows in synthetic biology. The invitation to this important international event was given in recognition of Dr. Haynes’ participation at the leading edge of synthetic biology and her high-impact contributions to the field.

PhD Defense – Congratulations to Rene Daer

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Rene_PhD_defenseBiological Design PhD student Rene Daer just successfully defended her thesis “Expanding Applications of Portable Biological Systems: Enhancements to Mammalian Gene Editing and Bacterial Quorum Sensing” today at 3 – 5 pm in Biological Design Auditorium B. Thank you to all of the friends, family, and colleagues who came to show their support.

This day is especially exciting since Dr. Rene Daer will my (Dr. Haynes’) first PhD graduate. On behalf of the Haynes lab, I hope this training experience launches a fun and fruitful career!