Katrin Karbstein, Ph.D.

Ribosome homeostasis via ribosome assembly and repair

Research Keywords: Ribosome homeostasis, ribosome assembly, ribosome remodeling, ribosome repair, genetics, biochemistry, structural studies, cancer, aging.

Research Specialty: How do cells maintain enough functional ribosomes.

Research Description: Ribosome produce proteins in all cells.

Ribosomes are the large macromolecular machines that produce proteins in all cells. Having too many, or too few ribosomes, or misassembled ribosomes alters protein homeostasis and is associated with diseases, including cancer. Thus, assembly of these structures from its ~80 constituents is highly regulated and quality controlled. Moreover, ribosome integrity is monitored continuously, and defective ribosomes are either repaired or degraded.

The Karbstein lab is dedicated to understanding how cells assembly ribosomes, what mechanisms for quality control exist, how defective ribosomes are detected and then either repaired or degraded. Moreover, we are studying alterations in ribosome composition in physiological as well as pathological circumstances including cellular stress, aging and cancer.

Current projects in the lab include:

1. Deciphering how cells avoid misfolding of ribosomal RNA to produce >1000 ribosomes per minute.
2. Delineating pathways of quality control that ensure newly-made ribosomes do not make mistakes during protein synthesis.
3. Studying ribosome remodeling during cellular stresses, and how this affects protein translation, stability and function.
4. Investigating the role of rRNA modifications in cancer.

We use a multi-disciplinary approach including biochemistry, genetics, genomics, proteomics, and structural biology. The lab is part of the Cancer Cell Biology Program within the Vanderbilt-Ingram Cancer Center, the Vanderbilt Institute of Chemical Biology, and Department of Biochemistry.

Significance: Since proteins carry out nearly all cellular functions, in addition to providing the scaffolds that cells use to communicate with other cells, adopt their shape, move, and divide, it is critical that cells produce these proteins correctly, in the right amount and at the correct time. Alterations in ribosomes or in ribosome number perturb this protein homeostasis, and are associated with diseases, including cancer, aging and neurodegenerative diseases. Thus, better understanding how cells maintain ribosome homeostasis is critical for developing a better understanding of the etiology of these diseases, develop novel diagnostic tools, as well as identify new therapeutic avenues.

Postdoctoral Position Availability and Details: Postdoctoral positions are available in the areas of ribosome assembly, ribosome quality control, ribosome repair, changes in cancer and aging. Please submit a CV and three letters of recommendation.