Carnegie Mellon University

Marcel Bruchez

Marcel Bruchez

Associate Professor of Chemistry, Biological Sciences, Biomedical Engineering (by courtesy), and Lane Center for Computational Biology (by courtesy)
Director of Molecular Biosensor and Imaging Center

Research

The Bruchez lab's research is focused on the development and use of new imaging tools to understand regulation of protein synthesis, trafficking and degradation using fluorescence microscopy approaches ranging from single molecule to whole animal imaging.  We use a new biosensor technology that we have developed based on fluorogen activating peptides to address two core questions:

1. What is the influence of ribosome translation dynamics on the fold and function of nascent proteins. The ribosome is the central machinist of the cell, crafting specific folded, functional proteins from the encoded genetic information. In this process, there are many similar ways to encode an identical protein sequence, but in practice these “identical” proteins often have distinguishable functional properties. Using single molecule imaging of fluorogen activating proteins on ribosomes, along with new peptide nucleic acid-based ribosome labeling we are studying the impact of ribosome stalling on the production of functional protein in mammalian and eukaryotic cell-free translation systems. These processes have been shown to play role in ion channel diseases such as cystic fibrosis and in drug resistance in human tumors.

2. Once membrane proteins are synthesized, they get sent to the cell surface, but how are they retained there. The secretion, endocytosis, recycling and degradation of membrane proteins is a tightly regulated process, yet the details of this regulation remain as central question in biology.  Using new biosensors that report on cellular physiology, we are studying the regulation of receptors, channels and transporters important in cardiovascular and neurological disorders to better understand and manipulate these pathways.

Publications

Grover, Anmol; Schmidt, Brigitte F.; Salter, Russell D.; Watkins, Simon C.; Waggoner, Alan S.; Bruchez, Marcel P. Genetically Encoded pH Sensor for Tracking Surface Proteins Through Endocytosis. Angewandte Chemie (International Ed in English) May 14, 2012, 51, no. 20: 4838–4842. doi:10.1002/anie.201108107.  PMID: 22461279

Maji, Suvrajit; Bruchez, and Marcel P. Inferring Biological Structures From Super-Resolution Single Molecule Images Using Generative Models. PLoS ONE 2012, 7, no. 5: e36973. doi:10.1371/journal.pone.0036973. PMID: 22629348

Shruti, S.; Urban-Ciecko, J.; Fitzpatrick, J. A.; Brenner, R.,;Bruchez, M. P.; Barth, A. L. The Brain-Specific Beta4 Subunit Downregulates BK Channel Cell Surface Expression. PLoS ONE 2012, 7(3), e33429. doi:10.1371/journal.pone.0033429

*Yushchenko, Dmytro A; Zhang, Ming; Yan, Qi; Waggoner, Alan S.; Bruchez, Marcel P. Genetically Targetable and Color-Switching Fluorescent Probe. Chembiochem. European Journal of Chemical Biology July 23, 2012, 13, no. 11: 1564–1568. doi:10.1002/cbic.201200334. PMID: 22777954