Lab Profile by Christi Binkley, CMB Graduate Student
What relates the fields of synthetic biology and transcriptional mechanisms? Answer: gene regulation. The Landick lab studies prokaryotic gene regulation to answer basic and applied research questions, using a variety of biochemical and genetic approaches. While the detailed nature of RNA polymerase (RNAP) is the foundational focus of the lab, new projects are constantly arising, ranging from transcription-translation coupling to genetic engineering for biofuel production.
RNAP is a multi-subunit enzyme responsible for transcribing RNA from DNA in all domains of life. During transcription, sequences of DNA can induce pausing of RNAP, which is a key aspect of transcription regulation. Even viruses are regulated by RNAP pausing, such as HIV-1, where pausing near the promoter allows time for a transactivator protein to bind and stimulate transcription of the viral genome1. The dynamic nature of transcription and the trans factors that regulate it are an exciting avenue of microbial research.
The exploration of RNAP has also generated collaborations across campus. Together with Dr. Aaron Hoskins, CMB trainer in the Department of Biochemistry, new single-molecule microscopy techniques are being developed to look at yeast RNAPII interactions with spliceosome components. Proteins and nucleic acids labeled with fluorophores can be visualized interacting with RNAPII using a technique called CoSMoS (colocalization single-molecule spectroscopy) to study recruitment of the spliceosome during transcription.
Robert Landick was initially trained as an organic chemist. Early on, Robert was inspired by the work of Dr. Gobind Khorana, a professor at UW-Madison. Khorana was the first to chemically synthesize oligonucleotides and thus create a synthetic gene, which could be used by bacteria2. His work at UW-Madison lead to a Nobel Prize, and Khorana is the namesake of the auditorium in the Biochemistry Labs building on campus. This research showed Robert that “the potential for synthetic biology is unlimited,” thus beginning his journey into bacterial biochemistry.
During the Landick lab’s 22 years at UW-Madison, the biochemistry and gene expression studies have expanded to also include metabolic engineering. Using the bacteria Zymomonas mobilis, the lab is interested in fine-tuning metabolic pathways to maximize isobutanol production, a next-generation renewable energy source. Funded by the US Department of Energy, and in collaboration with the Great Lakes Bioenergy Research Center, optimizing renewable bioproduct and biofuel production is an innovative future direction for US energy production.
On campus, the Landick lab enjoys a beautiful view of Lake Mendota from the 5th floor of the Microbial Sciences Building. The lab is large, with researchers from all corners of the globe, and from all different scientific backgrounds. The diversity of skills and knowledge is one of the many assets that has promoted research growth and innovation in the lab. Outside of science, the lab enjoys many traditions like our annual March Madness picnic, a lab retreat off-campus, and sending out a lab holiday card to our friends and collaborators every winter.
To learn more about research in the Landick Lab, visit: https://landick.wisc.edu/
Palangat, M., Meier, T. I., Keene, R. G., & Landick, R. (1998). Transcriptional pausing at+ 62 of the HIV-1 nascent RNA modulates formation of the TAR RNA structure. Molecular cell, 1(7), 1033-1042.
Review of Khorana’s work: Kresge, N., Simoni, R. D., & Hill, R. L. (2009). Total synthesis of a tyrosine suppressor tRNA: The work of H. Gobind Khorana. Journal of Biological Chemistry, 284(22), e5-e5.