Erin Heim, Ph.D.
My Latest Research
As a postdoctoral researcher, I was working under the guidance of Dr. Christina Woo. My research lab focused on developing new probes and amino acids that allowed for us to dissect protein-protein interactions on a global scale.
I pursued my Ph.D. under the mentorship of Dr. Daniel DiMaio. I have completed one project (LIL proteins) and was actively involved in the follow-up projects stemming from that publication. I also worked on two other projects as described below.
Biologically active LIL proteins built with minimal chemical diversity
Most proteins are long polymers of amino acids with 20 or more chemically distinct side-chains, whereas transmembrane domains are short membrane-spanning protein segments with mainly hydrophobic amino acids. We have defined the minimal chemical diversity sufficient for a protein to display specific biological activity by isolating artificial 26-aa-long transmembrane proteins consisting of random sequences of only two hydrophobic amino acids, leucine and isoleucine. A small fraction of proteins with this composition interact with the transmembrane domain of a growth factor receptor to specifically activate the receptor, resulting in growth transformation. These findings change our view of what can constitute an active protein and have important implications for protein evolution, protein engineering, and synthetic biology.
A novel screening technique to block viral infection and identify proteins involved in infectivity
Recent developments in high-throughput screening methods, such as RNA-based CRISPR or chemical modulator screens, have been critical to our current understanding of various cellular functions. However, cell death due to a crucial gene knockouts or lack of chemical specificity limits the success of these screens. A traptamer based screening method could help to overcome some of these limitations due to the remarkable specificity of these small proteins and their potential to create non-productive interactions with transmembrane proteins without removing the gene entirely. I am testing the ability of transmembrane protein aptamer (traptamer) libraries to be used as a novel genetic interference screening tool by screening for HPV infection inhibition. Although a high-throughput screen has been performed to identify cellular factors involved in HPV infection, there are still many unknown factors, such as the cell-surface receptor required for HPV entry. A traptamer-based screen for inhibition of HPV infection is an ideal supplement to current screens as it may select for crucial membrane proteins without the added limitation of RNAi toxicity or extensive disruptions of the protein’s endogenous function. After identifying traptamers that block HPV infection, additional biochemistry can be done to determine the proteins that interact with these traptamers to lead to the block in viral infection.
Isolating traptamers with activity that never naturally evolved
Previously the DiMaio lab has shown that traptamers can i) activate the platelet derived growth factor β receptor and transform cells, ii) activate the erythropoietin receptor and induce stem cell differentiation, and iii) down-regulate the CCR5 receptor, inhibiting HIV infection. These three processes mimic naturally occurring events and provide insight into the activity of the receptors since the traptamers are small, simple, and easily mutated. However, a question that remains is whether traptamers can be isolated which have an activity that has not come to exist in the natural course of evolution. I am using ErbB2 induced cell growth as a screen for biological activity that does not naturally occur since there is no ligand for ErbB2 homodimers. This project has the potential to show that traptamers can perform activities that have not arisen through evolution. Using the novel activity provided by this traptamer, we may gain insight into the functions and signaling cascades of ErbB2 that have not yet been studied due to a lack of any known homodimer activators. This study could also provide further evidence that traptamers can serve as tools for studying numerous and varied activities associated with membrane bound receptors.
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