*** I'm hiring! ***

1) Undergraduate or graduate students for individual investigation, rotation, honor's theses or sophomore research projects. Students do not necessarily have to be Physics majors, and a background in Chemistry, Biochemistry, Computer Science and Molecular Biology is also highly welcome. Students just need to have a broader interest in single-molecule biophysics, molecular biology or biochemistry. Several projects are available depending on the student's backgrounds. Inquire fro more information.

2) PhD projects: Several projects are available for students from various backgrounds including physics, chemistry (polymer chemistry, physical chemistry, or biochemistry), and biology (molecular), bioengineering, pharmacology or related subjects.
If you are not admitted to a graduate program at Kent State, yet: Please be aware that at US universities, students need to be accepted to a graduate program, do some courses and pass “candidacy exams” prior to starting full-time research for their PhD project. Typically, you will also be a teaching assistant in a course or lab during the semester. If your previous degree is not in Physics, you may also check the graduate programs of the "Biomedical Sciences" program, particularly the Cell & Molecular Biology program, or the Material Science Graduate Program.

Research Focus

Why Building with DNA?

DNA is a unique polymer. It is the information storage molecule of all known life forms, but can also be used to build up complex, artificial structures that are not found in Biology. Our group is leveraging this programmability to engineer nanoscale architectures and tools for applications in Biophysics and Structural Biology.

DNA-Lipid Nanodiscs as Tools for Single-Molecule Cryo-EM of Membrane proteins

A main focus of our group is to develop molecular tools that allow to study membrane proteins (MPs), which are among the most important, but least understood components of cells. All cells are surrounded by lipid membranes that are almost impermeable for water, salts or nutrients that cells need. For this reason, a large number of membrane protein(MPs) are inserted into the membranes that control cellular functions such as material transport, sensing, intercellular communication, cell adhesion, and energy conversion. MPs are also the targets for many therapeutic drug molecules. Knowledge of the molecular structure of MPs is necessary to understand the underlying molecular mechanisms of their function and can guide the development of therapeutic drugs for many common diseases. However, MPs are difficult to study and therefore the molecular structure of most MPs is still unknown. The goal of this project is to develop broadly applicable new tools using DNA nanotechnology that will facilitate solving MP structures with cryo-electron microscopes. [Nanoscale 2018].

Update 3/2021: Our lab recently received an NSF EAGER award for developing our DNA-lipid nanodiscs into tools for single-molecule cryo-EM tools for membrane proteins.

Update 8/2021: We received a major 5-year award from the National Institutes of Health (NIGMS R35) for this project.

Update 8/2022: We received an instrumentation grant for a highspeed Atomic force microscope to be installed in the Fall of 2022

Biophysics of Tightly Bent DNA

The nucleus of a human cell is only few micrometers long, but has to accommodate 2 meters of DNA. For this reason, cellular DNA is compacted in complex ways with DNA-binding proteins such as histones or by supercoiling to accommodate the limited available space. DNA compacting and the resulting high local curvature also plays a role in the regulation of gene expression and to protect DNA from mechanical damage.
Although DNA is arguably the best studied molecule in biophysics, the mechanics and dynamics of tightly bent DNA molecules such as DNA minicircles are not fully understood yet. Our lab combines experimental approaches including atomic force microscopy (AFM), single-molecule FRET (incollaboration with Hamza Balci's lab) and coarse grained molecular dynamics simulations (in collaboration with John Portman's lab) to discover exciting new behaviors of tightly bent DNA and intrinsically curved DNA sequences.

Other Research Interests

The projects below were primarily done in my previous lab in Dresden and are currently on ice until the group grows further

DNA-Based Plasmonic Devices

The field of plasmonics exploits the interaction of light with nanoscale metallic structures to confine, guide and manipulate light on scales below the diffraction limit. Plasmonic structures exhibit significant potential for applications including quantum optics, sensing, and short-distance optical communication (a). Towards this goal, we demonstrated the precise, robust, and high-yield assembly of gold nanoparticles on DNA origami templates (b).  [ACS Nano 2016].

More recently, we realized energy propagation through such a self-assembled waveguide to a fluorescent nanodiamond and out coupling of energy. We analyzed the waveguiding at a single-device level by electron energy loss spectroscopy (c) and cathodoluminescence imaging spectroscopy. Our work visually demonstrates the realization of nanometer-precise light manipulation and energy conversion. [Nano Lett. 2018].

Finally, these closely spaced gold nanoparticles create a strong plasmonic hotspot for the sensing of molecules. [Nano Lett. 2019].

Triangulated DNA Origami and Nanomechanical Actuators

In the macroscopic world, stiff and material-efficient structures such as construction cranes and high voltage transmission towers are usually built from triangulated wireframe structures. We extended the DNA origami concept to generate a series of triangulated trusses. These provide defined cavities that we seek to fill with functional elements. [Nano Lett. 2016].

By introducing single-stranded regions edges of the wireframe trusses, the structures are heavily deformed due to the entropic spring forces contracting the single-stranded region. The gaps can be filled by a gap filling polymerase (such as the T4 polymerase) or the addition of the missing oligonucleotides, thus creating a nanomechanical actuator. [ACS Nano 2018].

Outlook: This principle shall be the basis for stimuli-responsive mechanical nano devices in photonics or for applications in molecular biology. Moreover, we wish to determine biophysical properties such as their bending and torsional stiffness with super-resolution microscopy or optical tweezers.

Stabilizing DNA Structures for Nanomedicine

A main drawback of structural DNA nanotechnology is the instability of structures in biological environments. We developed a protection strategy based on block copolymer micellization which stabilizes DNA structures in biological or low-salt environments. [Angew. Chem. 2017].

Outlook: We will use this protection to enhance DNA-based nanomedicines.

“Next-Generation” DNA Synthesis Methods

Synthetic oligonucleotides (short single-stranded DNA) and genes (long double-stranded DNA) are the main cost factor for many studies in DNA nanotechnology, genetics and synthetic biology. Inexpensive chip-synthesized oligonucleotide libraries can contain hundreds of thousands of distinct sequences, however only at sub-femtomole quantities per strand. We developed a selective oligonucleotide amplification method based on rolling circle amplification (RCA) with a 10-1000-fold cost-reduction compared to synthetic oligonucleotides or competing amplification methods such as PCR. [Nat. Commun. 2015].

Outlook: We have recently extended our method for de novo gene synthesis. This will allow us to design custom scaffolds, and testing design principles that influence the folding kinetics and yields.

Group

Current group members:

• Praneetha Sundar Prakash (Research assistant, PhD candidate, Biomedical Sciences PhD Program)
• Soumya Chandrasekhar (Research assistant, PhD candidate, Chemical Physics Interdisciplinary Program)
• Draven Houser (PhD candidate, Physics)
• Dr. Sanjai Karanth (Postdoc, Biophysics)
• Philip Dudones (Undergraduate research assistant, Honor's thesis, Physics)
• Holly Matthew (Undergraduate research assistant, Honor's thesis, Physics)
• Ahmed Barghout (Undergraduate research assistant, Honor's thesis, Chemistry)
• Daniel Hollis (Undergraduate research assistant, co-supervized by Dr. John Portman)
• Thomas Swope (Graduate research assistant, co-supervized by Dr. John Portman)

Alumni:

Group photo December 2020

Further Reading

For more information, I recommend this 3-hour lecture (iBiology) by William Shih:

https://www.youtube.com/watch?v=Ek-FDPymyyg

https://www.youtube.com/watch?v=noWkRxKYBhU

https://www.youtube.com/watch?v=5cmg1oa4-fg

or a current review on structural DNA nanotechnology such as: DNA Origami: Scaffolds for Creating Higher Order Structures.

Teaching Advertisement

Fall 2023: Introduction into Single-Molecule Biophysics

Students who don't need this course for credit could audit. Students from other majors can get exceptions from their undergraduate advisors. Please inquire by email.