Research – bioRxiv Pre-print – Use of MYB as a new synthetic activator to enhance transgene expression within repressed Polycomb chromatin
Use of MYB as a new synthetic activator to enhance transgene expression from within repressed Polycomb chromatin
Barrett CM, McCracken R, Elmer J, Haynes KA. (2018) bioRxiv. https://doi.org/10.1101/487736
This work was inspired by a problem faced by many bioengineers who are interested in adding new, synthetic genes to human cells to fight disease, produce therapeutic proteins, and regenerate tissues and organs. New genetic material that is delivered into cells generally starts out working quite well: it is transcribed and translated like, or even better than, a “normal” gene. But eventually the synthetic gene is often shut down (silenced) by a DNA packaging and regulation system called chromatin. In our paper, we report the results of a project where we tested different DNA and protein components for their ability to protect synthetic genes from silencing. We use a priori knowledge of chromatin features at the synthetic gene to understand the mechanism of reactivation.
Congratulations to Haynes lab undergraduate researcher Luis Sanchez De La Vegas Covarrubias, who was selected for a position as a Mayo Clinic Special Research Student at Mayo Clinic, Scottsdale in Arizona, starting January 4, 2019. This highly selective program is being organized by the Mayo Clinic College of Medicine and Science (MCCMS).
Dr. Haynes has been invited to the University of California Santa Cruz to present a talk entitled “Development and application of synthetic chromatin-binding proteins for cell biology research” for the Molecular, Cell & Developmental Biology Department seminar series on Friday, November 2, 2018 in the Natural Sciences Annex 101.
Cassandra Barrett (Haynes lab PhD student, Biological Design) and Dr. Karmella Haynes will be presenting their latest work at the 2nd Epigenetics and Bioengineering Conference (EpiBio 2018) in San Francisco, CA at the Mission Bay Conference Center on October 4 – 6. The conference is presented by the Society for Biological Engineering (SBE). A great line-up of research talks and posters will include work from engineers and scientists who are applying the discipline of bioengineering to epigenetics. Cassandra Barrett will present a talk entitled “Active versus Accessible: Engineering Open Chromatin in Mammalian Cells.” Dr. Haynes will present a talk on “Histone-Binding Domains as Modules for Custom Fusion Proteins.” Registration is still available online, or attendees can register on site.
Dr. Haynes has been invited to the Fred Hutchinson Cancer Research Center to present a talk entitled “Investigating the behavior and impact of rationally-designed histone ‘readers’ in the context of cancer epigenomes” for the Current Biology Seminar series on Tuesday, October 2, 2018 in Pelton Auditorium. The seminar will be hosted by the Basic Sciences Division.
Unlocking access to DNA in chromatin
Barrett C and Haynes KA (2018) Chemical Engineering Progress. https://www.aiche.org/resources/publications/cep/2018/september/unlocking-access-dna-chromatin
Since the early 1970’s when scientists first began using bacterial enzymes to cut purified “naked” DNA, scientists have further developed bacterial enzyme-based systems to target and edit specific DNA sequences in eukaryotic hosts, including human cells. However, DNA within eukaryotic cells is not always fully exposed. Instead, it is packed into DNA/protein complexes that form a structure called chromatin. This review highlights new technologies that have enabled scientists to better understand and manipulate the chromosomal structures that impede or enhance access to the underlying DNA.
Haynes lab PhD students Cassandra Barrett and Stefan Tekel, as well as PI Dr. Haynes will present the lab’s latest work in human cell engineering at the 2018 Fall Retreat for the Engineering Biology Research Center (EBRC) at Colorado State University. Dr. Haynes serves on the governing board as a Councilor and has been affiliated with EBRC (formerly SynBERC) since 2011. Cassandra Barrett is the President of the Student and Postdoc Association, and the Policy & International Liaison. Dr. Haynes will present a talk entitled “BifC-PD: Fluorescent Sensors to Illuminate the Impact of Chromatin on the Nuclear Uptake and Expression of Recombinant DNA.” Cassandra Barrett will present a poster entitled “Active versus Accessible: Engineering Open Chromatin in Mammalian Cells.” Stefan Tekel will present a poster entitled “A Versatile Phenotypic Reporter for Cas9 Base Editing of Disease Relevant SNPs,” a collaborative project with the Brafman lab at ASU.