Erik Holmstrom
- Assistant Professor
Contact Info
1200 Sunnyside Ave
Lawrence, KS 66045
Personal Links
Biography —
Growing up in Western Montana, I was always drawn to the wonders of the natural world, particularly those aspects that were either so large or so small that they were hard to conceptualize. I distinctly remember when I first learned that molecules—infinitesimally small yet infinitely abundant—required a special number to be quantified.
Then, in 2008, as a senior majoring in Biology and Chemistry at Willamette University, I learned that modern technology had recently unveiled a new scientific frontier: the ability to study not just moles of molecules, but single molecules themselves. My mind was blown! I spent the next six years of my life at the University of Colorado, where I used these so-called single-molecule techniques to study how RNA molecules fold up into intricate three-dimensional structures with important biochemical functions.
After earning my PhD in 2014, I moved to Zurich, Switzerland, to use these same techniques to better understand the conformational dynamics of several RNA-protein complexes. In 2019, I brought my passion and expertise to Lawrence, KS, where I established my own single-molecule research program as an Assistant Professor in the Department of Molecular Bioscience.
Education —
Research —
Single-molecule biophysical studies of RNA-protein interactions
Interactions between nucleic acids and proteins form the foundation of the central dogma of molecular biology. The functional importance of these biomolecules hinges on their ability to sample multiple conformations. By studying these dynamic structure-function relationships, we are able to identify the mechanisms that govern the biochemical processes arising from these nucleic acid-protein interactions.
This notion is also perfectly applicable to viruses, which can be crudely approximated as infectious sub-micrometer particles consisting of genetic material encapsulated by proteins, forming a so-called nucleocapsid. For example, assembly of the hepatitis C virus (HCV) nucleocapsid depends on interactions between the genomic RNA and numerous copies of the multifunctional core protein. Preventing these interactions represents a promising approach to inhibit HCV assembly. However, this approach has not been thoroughly explored because the structure-function relationship associated with the assembly process is not well understood.
One of the goals of our lab is to use concepts from biology, chemistry, and physics to provide a molecular description of the HCV assembly pathway by studying the structural and functional aspects responsible for RNA-induced formation of HCV nucleocapsid-like particles (NLPs).
Although there are a number of established experimental techniques that can be used to tackle this challenge, most of them are complicated by heterogeneous biological samples and asynchronous molecular behavior. The complications associated with these ensemble techniques can be avoided by studying single molecules. In particular, single-molecule FRET is an ideal experimental approach for these types of investigations because it simultaneously reports on the structural, energetic, and kinetics properties of fluorescently-labeled biomolecules. Accordingly, our lab uses these single-molecule methods, in conjunction with conventional ensemble techniques, to study a variety of nucleic acid-protein interactions.
For more information see The Holmstrom Lab website.
Teaching —
- BIOL 636 - Biochemistry I (fall every year)
- BIOL 750 - Advanced Biochemistry (spring odd-years)
- BIOL 918 - Modern Biochemical & Biophysical Methods (spring even-years)
My classroom teaching activities are associated with lecture courses tailored to junior and senior biochemistry majors, as well as upper-level courses for graduate students across campus with interests in biochemistry and biophysics.
Additionally, I spend a substantial amount of time mentoring and directing the research activities of undergraduate, graduate, and postdoctoral trainees with a wide range of personal, academic, and scientific backgrounds. As a result of these teaching efforts, trainees have gone on to pursue their educational goals in graduate school and medical school, or their professional goals in the biomedical research industry.
Selected Publications —
See all papers by Erik D Holmstrom on PubMed
- Sperstad PD, Holmstrom ED*. “Conformational Dynamics of the Hepatitis C Virus 3ʹX RNA ” RNA (2024) under review
- Nepal S, Holmstrom ED*. “Single-molecule-binding studies of antivirals targeting the hepatitis C virus core protein.” J. Virol. (2023) DOI: 10.1128/jvi.00892-23
- Sanders JC, Holmstrom ED*. "Integrating single-molecule FRET and biomolecular simulations to study diverse interactions between nucleic acids and proteins" Essay Biochem. (2021) DOI: 10.1042/EBC20200022
- Sharma R, KK S, Holmstrom ED*, Westerlund F*. "Real-time Compaction of Nanoconfined DNA by an Intrinsically Disordered Macromolecular Counterion" Biochem. Biophys. Res. Commun. (2020) DOI: 10.1016/j.bbrc.2020.06.051
- Holmstrom ED*, Liu Z, Nettles D, Best RB, Schuler B*. “Disordered RNA chaperones enhance nucleic acid folding via local charge screening.” Nat. Commun. (2019) DOI: 10.1038/s41467-019-10356-0
- Holmstrom ED, Nettels D, Schuler B*. "Conformational Plasticity of Hepatitis C Virus Core Protein Enables RNA-Induced Formation of Nucleocapsid-like Particles." J. Mol. Biol. (2018) DOI: 10.1016/j.jmb.2017.10.010
- Vieweger M, Holmstrom ED, Nesbitt DJ*. "Single-Molecule FRET Reveals Three Conformations for the TLS Domain of Brome Mosaic Virus Genome." Biophys J. (2015) DOI: 10.1016/j.bpj.2015.10.006