Marcelo C. Sousa
Professor

Office: JSCBB A417
Lab: JSCBB A480 
Lab Phone: 303-735-6334
Fax: 303-492-5894

Education

PhD: University of Buenos Aires, 1995
PharmD: University of Buenos Aires, 1989
Postdoctoral Fellow: School of Medicine Stanford University, 1995-2001

Areas of Expertise

Electron Cryo-Microscopy (cryo-EM), Membrane Biology, Molecular Biophysics, Proteins and Enzymology, Single Molecule Biology, and Structural Biology.

Awards and Honors

  • 2004-2008 New Scholar in Global Infectious Disease, The Ellison Medical Foundation
  • 2003-2005 Scientist Development Award, American Heart Association
  • 2003 Junior Faculty Development Award, University of Colorado Boulder

Structural Biology

Our research program seeks to understand, in molecular detail, fundamental cellular processes that occur at the membrane interface. We utilize a multidisciplinary approach in our program. X-ray crystallography and EM are our main tools to obtain high-resolution structures and macromolecular mechanisms are elucidated with complementary biochemical and biophysical approaches including single molecule studies. Current projects include:

(i) Modification of the Bacterial Outer Membranes Mediating Antibiotic Resistance: Lipid-A modification with Ara4N and pEtN confers resistance antimicrobial peptides of the innate immune system as well as antibiotics such as colistin. The focus of our research is to determine the structure and mechanism of enzymes essential for Lipid-A modification with Ara4N and pEtN as a key for the design and evaluation of specific inhibitors.

(ii) Folding and Insertion of Membrane Proteins in the Bacterial and Mitochondrial Outer Membrane: We seek to understand the molecular mechanisms by which chaperones and the BAM membrane protein complex cooperate to promote folding and specific insertion of -barrel OMPs into bacterial and mitochondrial outer membranes.

(iii) Molecular Determinants of protein secretion: We aim to define the molecular signatures that allow proteins to be unfolded and secreted by the Type Three Secretion System.

See my NCBI bibliography for a full and up-to-date list.

  • Sousa MC. New antibiotics target the outer membrane of bacteria. Nature. 2019 Dec;576(7787):389-390. doi: 10.1038/d41586-019-03730-x. PubMed PMID: 31844257
  • LeBlanc MA, Fink MR, Perkins TT*, Sousa MC*. Type III secretion system effector proteins are mechanically labile. Proc Natl Acad Sci U S A. 2021 Mar 23;118(12). doi: 10.1073/pnas.2019566118. PubMed PMID: 33723050. *co-corresponding Authors.
  • Mitchell ME, Gatzeva-Topalova PZ, Bargmann AD, Sammakia T, Sousa MC. Targeting the Conformational Change in ArnA Dehydrogenase for Selective Inhibition of Polymyxin Resistance. Biochemistry. 2023 Jul 18;62(14):2216-2227. doi: 10.1021/acs.biochem.3c00227. Epub 2023 Jul 6. PubMed PMID: 37410993.