We have two primary research directions that rely on a combination of biochemical, biophysical and single molecule methodologies.
1.) The first research direction is focused on understanding the physical properties of eukaryotic genomes and how these properties function with biochemical regulation to control gene expression.
Eukaryotic genomes are organized by being repeatedly wrapped around histone protein octamer to form long chains of chromatin. This results in the 1 meter long human genomic DNA being wrapped into about 20 million nucleosome spools.
Nucleosome Structure (PMID: 1KX5)
Chromatin and nucleosome undergo structural changes, which are key to controlling what regions of the genomic DNA is accessible to gene regulator complexes. These structural changes are regulated by a wide range of epigenetic factors including histone post translational modifications, and protein regulator complexes including transcription factors and transcription co-activators. These all function in combination to determine which genes are active and which genes are silent, and is central to cells functioning correctly. We have a number of ongoing project focused on pioneer transcription factors, transcription co-activators, histone post-translational modifications, and linker histone H1. Below is an image of a nucleosome bound by the budding yeast pioneer factor that was solved in collaboration with Song Tan’s lab and Lucy Bai’ lab. They are both at Penn State.
A nucleosome bound by the budding yeast pioneer factor that was solved in collaboration with Song Tan’s lab and Lucy Bai’ lab. They are both at Penn State.
2.) The second research direction is focused on using DNA nanotechnology to develop new nanoscale devices out of DNA to function as molecular sensors and even robots.
Scaffolded DNA origami is an approach that allows for the self-assembly if highly complex devices on the 10 to 100 nanometer length scale with atomic precision. By engineering region of the nanodevice to contain double stranded and single stranded DNA, the device can have stiff and flexible regions. This allows for devices such as nanoscale hinges and rotors to be created out of DNA. In addition, these device can be attached to other biomolecules and even inorganic particles including gold. We are designing and characterizing devices for (i) studying biomolecular complexes including chromatin, (ii) targeting DNA nanodevices to cells, (iii) developing hybrid devices composed of DNA and inorganic nanoparticles, and (iv) generating devices with new sensing functions. Below are images of a nanocaliper device we are using to study nucleosomes and chromatin.