Assistant Professor, University of Minnesota Department of Genetics, Cell Biology, and Development
420 Washington Ave SE
Minneapolis, MN 55455
Office phone: 612-625-1950
The research in the Engelhart laboratory is directed towards better understanding nucleic acid folding and function in order to advance two broad themes: 1) the development of novel nucleic acid-based imaging, analytical, and diagnostic technologies and 2) the elucidation of unanticipated roles for nucleic acids in vivo.
Theme 1: GFP and other fluorescent proteins have enjoyed over twenty years of extraordinary success as tools for cellular and whole-organism imaging and readout. In the late 1990’s, it was shown that this protein could be fused to an RNA-binding protein from the MS2 bacteriophage and used to image RNA within cells. This approach has numerous downsides, however, including the fact that the parent MS2 protein is trafficked to the nucleus, and it exhibits a high background as a result of diffuse GFP signals from non-localized GFP. Thus, a great deal of interest has developed in the last few years in direct imaging of RNA using aptamers selected de novo that promote fluorescence of a cognate small molecule ligand that is not fluorescent except when bound to its aptamer target. With robust aptamers capable of doing this, RNA could be imaged directly with inherent low background fluorescence. We are working towards engineering and selecting brighter, more photostable, better-folding aptamers (and improved small molecule ligands for these aptamers) that are capable of allowing us to directly probe arbitrary RNAs of interest in complex systems, such as primary neuron cultures and whole model organisms.
Theme 2: A wide range of nucleic acid structures exist beyond the well-known extended Watson-Crick duplex. Noncanonical secondary structures, such as four stranded G Quadruplexes, are formed by the G-rich (TTAGGG)n repeat found in the vertebrate telomere sequence, numerous promoters for proto-oncogenes, such as c-myc and c-kit, and the BCL2 major breakpoint region of the t(14;18) translocation in follicular lymphoma. Recently, Lin28, in addition to its well-known role in regulation of let-7 maturation, was observed to act as a nucleic acid folding chaperone, remodeling quadruplex nucleic acids. Similarly, even duplex DNA can exhibit noncanonical structures, such as supercoiling, as found in plasmids and DNA undergoing replication, and condensation, as observed in chromatin. Our laboratory is studying the roles of noncanonical nucleic acid structures in regulation of gene expression and their possible roles in disease states.
Our laboratory uses a wide range of techniques spanning the spectrum from chemistry to biology, from microscopy and cell/tissue culture to biophysics and organic chemistry.
I attended Arizona State University in Tempe, Arizona, where I received my B.S. There, I worked in the laboratory of Ian R. Gould, where I studied the photochemistry of DNA-binding small molecule drugs. During this time, I also worked for a summer in the laboratory of David M. Ferguson at the University of Minnesota in Minneapolis, Minnesota synthesizing small molecule opioid ligands. Following my undergraduate training, I attended the Georgia Institute of Technology in Atlanta, Georgia from 2005 to 2010, where I earned my PhD in the laboratory of Nicholas V. Hud. There, I studied self-assembling polymers, nucleic acids biophysics, and the origins of life. From 2011 to 2016, I was a postdoctoral fellow in the laboratory of Jack W. Szostak at the Massachusetts General Hospital/Harvard Medical School in Boston, Massachusetts, where I researched functional nucleic acids and lipid vesicles, with a particular interest in discovering and developing unexpected catalytic and functional behaviors of these molecules and assemblies. Since 2016, I have been an Assistant Professor in the University of Minnesota Department of Genetics, Cell Biology, and Development (GCD). My research is directed towards better understanding nucleic acid folding and function in order to advance two broad themes: 1) the development of novel nucleic acid-based imaging, analytical, and diagnostic technologies and 2) the elucidation of unanticipated roles for nucleic acids in vivo.
Publications. I have written abstracts targeted to the lay public for each of my publications, which can be found at each publication’s webpage. Please feel free to contact me with any questions about my work.
- 2017, Stanley Miller Early-Career Research Award, International Society for the Study of the Origin of Life.
- 2014-2015, Tosteson Fellowship, Massachusetts General Hospital Executive Committee on Research
- 2011-2013, NASA Astrobiology Institute Postdoctoral Fellowship Award, National Aeronautics and Space Administration
- 2006, Texaco Fellowship Award, Georgia Institute of Technology
- 2005, Cherry Emerson Fellowship Award, Georgia Institute of Technology
- 2005, Barrett Honors College Thesis Support Award, Barrett, The Honors College at Arizona State University
- 2000-2004, National Merit Scholarship
Public Lectures (External Audiences, Non-Conference):
- “Functional Behaviors of Pre-RNA.”Carleton College. Northfield, MN. April 16, 2018.
- “Nucleic Acids Systems Chemistry: From the RNA world to the protocell.” Award Lecture for Stanley Miller Early-Career Research Award. International Society for the Study of the Origin of Life. San Diego, CA. July 20, 2017.
- “Emergent properties arising from biopolymer-membrane interactions.” Earth-Life Science Institute, Tokyo Institute of Technology, Tokyo, Japan. June 14, 2017.
- “Functional Interactions between Lipid Compartments and Nucleic Acid Catalysts.” School of Life Sciences, Tsinghua University, Beijing, China. June 9, 2017.
- “Minimal cellular systems: from catalysts in compartments to life as we know it.” Bard College Chemistry Division. Annandale-On-Hudson, NY. April 19, 2016.
- “Complex mixtures of prebiotic polymers: Consequences for replication, catalysis, and the emergence of life.” NASA Virtual Seminar – NPP Alumni Talk. May 5, 2014.
- “Replicating nucleic acids differently.” Harvard Department of Chemistry and Chemical Biology. Cambridge, MA. October 11, 2013.
- “Product Mixtures in Prebiotic RNA synthesis: Consequences for Functional RNAs.” BEYOND Center at Arizona State University. Tempe, AZ. May 29, 2013.
- University of Roma Tre. Rome, Italy. February 28, 2013.
Public Lectures (External Audiences, Conferences):
- “Novel Properties Arising from Interactions Between Lipid Compartments and Biopolymers.”Astrobiology Science Conference 2017. Phoenix, AZ. April 25, 2017.
- “Homeostatic Control of Ribozyme Activity Within Growing Model Protocells.” Gordon Research Seminar 2016. Galveston, TX. January 17, 2016.
- “What was in that Warm Little Pond? Consequences of Synthesizing Contemporary Biopolymers by Abiotic Chemistry.” Astrobiology Science Conference (AbSciCon) 2015. Chicago, IL. June 18, 2015.
- “Copying RNA in Primitive Cells: Overcoming Challenges and Discovering Opportunities.” Earth-Life Science Institute Chemistry Workshop, Cambridge, MA. February 27, 2015.
- “Nucleic acids with mixed backbones: fatal or beneficial for an RNA World?” Earth-Life Science Institute Chemistry Workshop, Tokyo, Japan. March 20, 2014.
- “Embracing the mess: Consequences of product mixtures in model prebiotic reactions.” Southeastern Regional Meeting of the American Chemical Society. Atlanta, GA. November 13, 2013.
- “Imperfect RNA synthesis via model prebiotic reactions and consequences for Functional RNAs.” Albany: Conversation 18. Albany, NY. June 12, 2013.
- “Potential Mechanisms of Prebiotic Gene Regulation.” Southeastern Regional Meeting of the American Chemical Society. Raleigh, NC. November 16, 2012.
- “2′,5′ substitution in catalytic and functional RNAs.” Astrobiology Science Conference (AbSciCon) 2012. Atlanta, GA. April 16, 2012.
- “A synthetically facile reversible linkage for nucleic acid ligation.” Southeastern Regional Meeting of the American Chemical Society. San Juan, Puerto Rico. October 22, 2009.
- “Nanomolar, selective G-quadruplex ligands from one pot: thermodynamic and structural studies of azacyanines.” Southeastern Regional Meeting of the American Chemical Society. Nashville, TN. November 14, 2008.
Public Lectures (Internal):
The below presentations were made to audiences at the University of Minnesota.
- “Fluorescent aptamers: rapidly developed sensors for arbitrary analytes of interest.” New Technologies to Detect Water Pollution Symposium. May 21, 2018
- “Hold the water! Probing nucleic acid hydration with alternative solvents.” Biophysics Seminar Series. April 12, 2018
- “Bioorganic nucleic acids chemistry in primitive and modern biology.” Chemical Biology Colloqium Series. October 24, 2016
- “Nucleic acids: How do they fold and how can we see them?” GCD Departmental Retreat. September 20, 2016.
- “Direct RNA imaging in living systems: challenges and opportunities.” Developmental Biology Center Meeting. September 16, 2016
The below presentations were made to the Simches Research Center community at Massachusetts General Hospital at building-wide seminars.
- “Nucleic acids in alternative solvents.” October 18, 2012.
- “Studies of a potential precursor to RNA.” March 23, 2012.
- Co-chair, Gordon Research Seminar, Origins of Life, 2018
- Section Organizer, AbSciCon 2015
- Discussion Leader, 2012 Origin of Life Gordon Research Seminar
- Editor, NASA Astrobiology Origin of Life Focus Group Website Features
- Co-Organizer, University of MN RNA Supergroup
- 2008-Present, American Chemical Society
- 2016-Present, Faculty Member, University of Minnesota RNA Supergroup
- 2016-Present, Member, University of Minnesota Masonic Cancer Center
Peer Review Activities (Journals):
- Angewandte Chemie
- Bioorganic and Medicinal Chemistry Letters
- Chemical Society Reviews
- Encyclopedia of Molecular Cell Biology and Molecular Medicine (Wiley)
- International Journal of Molecular Sciences
- Journal of Molecular Evolution
- Nature Chemical Biology
- New Journal of Chemistry
- Nucleic Acids Research
- Organic and Biomolecular Chemistry
- Physical Chemistry Chemical Physics
- Polymer Chemistry
- Scientific Reports
- The Science of Nature – Naturwissenschaften
Peer Review Activities (Funding):
- Georgia Institute of Technology President’s Undergraduate Research Award
- NASA Exobiology
- NASA Postdoctoral Program