Charles M. Deber

Charles M. Deber


BSc, Polytechnic Institute of Brooklyn, 1962
PhD, Massachusetts Institute of Technology, 1967
Postdoc, Harvard Medical School, 1968–70

Address Research Institute, The Hospital for Sick Children
Molecular Structure & Function
PGCRL, Room 20.9712
686 Bay Street
Toronto, ON M5G 0A4
Lab Deber lab
Lab Phone 416-813-5855
Office Phone 416-813-5924

Charles Deber was born and raised in Brooklyn, New York.  He received his BSc from the Polytechnic Institute of Brooklyn (working with Murray Goodman); his PhD in Organic Chemistry from MIT (Arthur Cope); and was a post-doctoral fellow at Harvard Medical School (Elkan Blout) and research associate at the University of Wisconsin-Madison Enzyme Institute (Henry Lardy).  He joined the Research Institute at the Hospital for Sick Children in 1976, with cross-appointment to the University of Toronto Department of Biochemistry. Dr. Deber was recognized by the American Peptide Society with the Vincent du Vigneaud Award in 2000 for “Outstanding Career Achievements in Peptide Research”, and the Murray Goodman Scientific Excellence and Mentorship Award in 2009.  At U. of T., he received the W.T. Aikins Award for excellence in undergraduate teaching in the Faculty of Medicine. Dr. Deber was elected in 2001 as a Fellow of the Royal Society of Canada (FRSC). Dr. Deber’s research utilizes natural and de novo designed hydrophobic peptides and proteins, and the application of spectroscopic techniques, molecular modeling, and bioinformatics, to investigate the interactions and structures of peptides and proteins within membranes, how membrane-embedded mutations underlie protein misfolding diseases, and how knowledge gained from these studies can be applied to the development of membrane-interactive peptide therapeutics.

In the News

Research Lab

Membrane proteins – either in low or non-supply, or with critical mutations – underlie the causes of many human diseases, including several forms of cancer, diabetes, multiple sclerosis, cystic fibrosis, and muscular dystrophy. Our central hypothesis is that key relationships between biological function and membrane protein structure can be defined through characterization of the transmembrane (TM) segments which comprise the membrane domains of proteins of proteins by several criteria, including composition, sequence, chain length, hydrophobicity, conformation, and elucidation of specific TM-TM interactions within membranes. As our fundamental understanding of the structures of membrane-based domains of proteins increases, we can implement this knowledge to the design and synthesis of novel antimicrobial peptides, and peptide inhibitors of bacterial multidrug resistance.

Learn more: Deber lab

Research Description

Peptide and Protein Structure in Membranes: From Folding to Drug Discovery

Membrane proteins are required for cellular processes such as nutrient uptake, signaling, and cell-cell communication. Through a series of model and designed membrane protein and peptide constructs, our lab studies how membrane proteins assemble to produce their biologically functional structures. Understanding these principles and mechanisms allows us to pinpoint sequence features required for membrane proteins to fold, and to use these to design peptide therapeutics. Several projects are underway:

Mutations in membrane proteins as the source of genetic diseases: The case of cystic fibrosis.

Protein-mediated human diseases are caused by mutations that change packing and/or electrostatic interactions needed for normal protein folding and function. For example, the most common cause of cystic fibrosis (CF) is deletion of the nucleotide binding domain residue F508 in the cystic fibrosis transmembrane conductance regulator (CFTR), which causes the protein to misfold. In addition to delta-F508, nearly 2,000 mutations have been identified by the CF Genetic Analysis Consortium – of which hundreds occur in the membrane domain of CFTR. Complete understanding of how mutations in membrane domains lead to CFTR misfolding is needed to develop better treatments. To this end, our lab has successfully expressed in E. coli helix-loop-helix constructs (‘hairpins’) corresponding to the membrane-spanning sequences of CFTR, and uses various spectroscopic methods such as fluorescence and circular dichroism to investigate their interactions with membrane environments. Our research focuses on both membrane-based sites and the intervening loops where CF-phenotypic mutations occur, with the goal of assessing the structural impact of point mutations on hairpin folding.


Secondary structure conversion in CFTR TM3/4 hairpins. Introduction of a Pro-Gly β-turn-promoting couplet into the wild type loop creates a steric clash (D), and converts the hairpin from a helix-loop-helix structure (A) to an oligomerized β-sheet structure (B,C) that interacts with lipid bilayers (E).

Peptide inhibitors of bacterial multidrug resistance

Bacterial resistance to drugs and toxic compounds is caused by pumps embedded in the bacterial cell membrane. The small multidrug resistance (SMR) protein family pumps drugs out of bacteria only when at least two inactive monomers assemble within the membrane. SMR monomers encompass four transmembrane (TM) α-helices connected by three extracellular short loops, and must use their TM helices to assemble. Disruption of these helix-helix interactions will therefore impair the ability of bacteria to efflux drugs. We have identified the key SMR helix-helix assembly motifs on TM4, and created peptide mimics of this helix-helix interface that reduce SMR activity in vitro and in vivo. These peptides are now lead compounds for development of peptide therapeutics with broad-spectrum inhibition activity. Peptide design concentrates on shortened analogs and ‘stapled’ peptides, where the functional conformation of the inhibitor peptide is locked into a ring.


Proposed drug efflux inhibition model for small multidrug resistance proteins (SMRs). The transmembrane (TM) dimerization site on SMR helix 4 is a “hotspot for inhibition”. A designed TM4 peptide competes for the dimerization site, producing monomers, and rendering the protein unable to transport a typical substrate.

 Antibiotic peptides active against bacterial biofilms

Chronic bacterial infections that occur in CF patients are difficult to treat because bacteria are resistant to existing antibiotics. Treating infections becomes even more difficult when bacterial attach to tissues or to other surfaces by producing exopolysaccharides (EPS), resulting in bacterial biofilms that are nearly impossible to eliminate. New ways to treat resistant infections are thus urgently needed. We have de novo designed and synthesized a new category of cationic antimicrobial peptides (CAPs) that effectively eliminate Pseudomonas aeruginosa – the primary cause of lung disease and mortality in CF patients. These new CAPs – epitomized by sequences such as KKKKKK-AAFAAWAAFAA-NH2 (termed 6K-F17), and featuring our patented implementation of charge segregation from the hydrophobic core, kill bacteria by destroying cell membranes rather than by targeting a specific protein or biochemical process. We are currently working to identify the best lead CAPs by testing their activity against resistant P. aeruginosa strains isolated from CF patients, and determining safety and pharmacokinetics in animal models. These studies will greatly advance our discovery toward the goal of clinical trials in CF patients.


Comparison of proposed mechanisms of action between the natural cationic antimicrobial peptide (CAP) magainin II amide (left) and the designed CAP 6K-F17 (sequence shown) (right). By segregating positive charges from the hydrophobic core segment of the peptide – instead of placing them on opposite faces as in the amphipathic magainin II amide – the membrane-destructive power of the designed CAPs is enhanced through their ability to “grip” and then “dip” into the anionic bacterial membrane, rather than being anchored into its surface.

Peptide models to study translocon recognition of transmembrane protein segments

Newly-synthesized helical membrane proteins insert into the lipid bilayer in a stepwise fashion through which individual helices are inserted sequentially with the aid of the translocon, an α-helical protein located in the plasma membrane of prokaryotes and the ER of eukaryotes. The translocon forms a channel through which passing nascent polypeptide segments partition laterally into the lipid bilayer. Insertion by the translocon is thought to be a biophysical event that can be modeled by in vitro methods that measure partitioning in membrane environments. To address these ideas experimentally, we are designing and synthesizing several series of peptides of length typically required to span a biological membrane, and using biophysical analysis to assess the relationship between sequence and partitioning in vitro.


Schematic model of translocon- vs. HPLC-mediated helix insertion. (A) The translocon crystal structure (T. thermophilus SecYE; PDBID: 2ZJS) is shown in red, inserting an ideal helix (blue). In (B), the protein helix partitions from an HPLC polar mobile phase into the C18 acyl regions (orange) of the column’s solid support, paralleling a bilayer insertion process.

Awards & Distinctions

1996 — W.T. Aikins Award for Excellence in Undergraduate Teaching, University of Toronto Faculty of Medicine
2000 — Vincent du Vigneaud Award for Outstanding Achievements in Peptide Research, American Peptide Society
2001 — Elected Fellow of the Royal Society of Canada (FRSC)
2001 — Elected to Canadian Who's Who
2009 — Murray Goodman Award for Scientific Excellence and Mentorship in Peptide Science

Courses Taught

BCH 2105H Cystic Fibrosis: The Cause, The Treatment
BCH 2024H Cystic Fibrosis: The cause, The treatment
BCH473Y Advanced Research Project in Biochemistry


View all publications on PubMed

Therapeutic design of peptide modulators of protein-protein interactions in membranes (Review).
Stone TA and Deber CM
Biochim. Biophys. Acta – Biomembranes 1859, 577-585 (2017).  Read

Hydrophobic clusters raise the threshold hydrophilicity for insertion of transmembrane sequences in vivo.
Stone TA, Schiller N, Workewych NV, von Heijne G, and Deber CM
Biochemistry 55, 5772-5779 (2016).   Read

Modulating transmembrane alpha-helix interactions through pH-sensitive boundary residues.
Ng DP and Deber CM
Biochemistry 55, 4306-4315 (2016).  Read

Structural impact of proline mutations in the loop region of an ancestral membrane protein.
Nadeau VG and Deber CM
Peptide Science 106, 37-42 (2016).  Read

Design and characterization of a membrane protein unfolding platform in lipid bilayers.
Nadeau VG, Gao A, and Deber CM
PLoS ONE 10, e0120253 (2015). doi:10.1371/journal.pone.0120253.  Read

Helix-helix interactions: Is the medium the message? (Invited “Preview” commentary).
Deber CM and Ng DP
Structure (Cell Press) 23, 437-438 (2015).   Read

Hydrophobic blocks facilitate lipid compatibility and translocon recognition of transmembrane protein sequences.
Stone TA, Schiller N, von Heijne G, and Deber CM
Biochemistry 54, 1465-1473 (2015).  Read

Efflux by small multidrug resistance proteins is inhibited by membrane-interactive helix-stapled peptides.
Bellmann-Sickert K, Stone TA, Poulsen BE, and Deber CM
J. Biol. Chem. 290, 1752-1759 (2015).  Read

Terminal residue hydrophobicity modulates transmembrane helix-helix interactions.
Ng DP and Deber CM
Biochemistry 53, 3747-3757 (2014).   Read

Functional response of the small multidrug resistance protein EmrE to mutations in transmembrane helix 2.
Wang J, Rath A, and Deber CM
FEBS Lett. 588, 3720-3725 (2014).   Read