"Engineering Human Chromatin-Based Systems for Programmable Control of Gene Expression"

This event is sponsored by FAMU-FSU Engineering Department of Chemical & Biomedical Engineering.

Abstract: The ability to regulate multiple genes across large genomic regions remains a central challenge in synthetic biology and bioengineering. Our lab is tackling this problem through epigenetic engineering, the rational design of chromatin-interacting proteins and long noncoding RNAs (lncRNAs) to achieve robust, scalable transcriptional control. I will present a series of synthetic biology platforms that illustrate how chromatin regulation can be both read and rewritten across diverse cell types. These include a triple-negative breast cancer (TNBC) biosensor cell line that detects cancer-aggravating serum factors via epigenetically triggered transgene repression, and a newly engineered histone methylation reader with enhanced affinity for H3K27me3. Building on these tools, we developed a modular library of synthetic transcriptional activators and tested their function in breast cancer cells, T cells, and macrophages as part of a summer course at Cold Spring Harbor Laboratory. Our latest cell engineering technologies feature lncRNA-based platforms for domain-level regulation of gene expression. Using sequence motifs from the X-chromosome-silencing lncRNA XIST, we constructed synthetic RNA scaffolds that silence genes in a time- and distance-dependent manner in human cells. In parallel, we designed a yeast model to dissect RNA-guided recruitment of chromatin modifiers, enabling high-throughput testing of RNA structure-function relationships. Surprisingly, we find that repression activity does not scale linearly with repeat number, highlighting the importance of synthetic design in tuning epigenetic responses. Together, these studies advance a synthetic framework for controlling genome-wide expression patterns, with implications for cell therapy, disease modeling, and epigenome engineering.

Karmella A. Haynes, PhD

Assistant Professor

Wallace H. Coulter Department of Biomedical Engineering

Emory University

Speaker Bio: Karmella Haynes is an Assistant Professor of Biomedical Engineering at Emory University. She earned her B.S. in Biology at Florida A&M University (1999), and her Ph.D. studying epigenetics and chromatin in Drosophila at Washington University, St. Louis. Postdoctoral fellowships at Davidson College and Harvard Medical School introduced her to synthetic biology. Her Davidson HHMI postdoc fellowship project on bacterial computers was recognized as “Publication of the Year” in 2008 by the Journal of Biological Engineering. Today, her research aims to apply the intrinsic properties of chromatin, the DNA-protein structure that packages eukaryotic genes, to engineer proteins and nucleic acids that control cell development. After Dr. Haynes joined the faculty at the Emory School of Medicine in 2019, she received an NIH R21 grant (2019) to develop new protein engineering and computational tools for cancer epigenetics, and launched the annual NSF-funded AfroBiotech conference series (2019). She is a founder and instructor of the Cold Spring Harbor Summer Course on Synthetic Biology (2013 - present), a member of the national Engineering Biology Research Consortium (EBRC, 2014 - present), past advisor and current Judge Emeritus for the annual International Genetically Engineered Machines (iGEM) competition (2007 - present), and a member of the NIH National Scientific Advisory Board for Biosecurity (2021). She was named one of 1000 Inspiring Black Scientists by Cell Mentor (Cell Press 2020), was a featured guest on PBS NOVA (2020) and PRI’s Science Friday (2008, 2016, 2025), was profiled in Forbes magazine (2020), received Color Magazine’s Women of Color: Innovator in STEM award (2021), and was elected into the 2023 American Institute for Medical and Biological Engineering (AIMBE) College of Fellows.