10th Annual PSFaM Conference

Lisa Craig

Simon Fraser University



Dr. Craig received a MSc and PhD from Simon Fraser University and trained with John Tainer at the Scripps Research Institute for her postdoctoral studies. She returned to Simon Fraser in 2005 as an Assistant Professor in the Molecular Biology and Biochemistry Department, where she is now Professor and Chair. Dr. Craig’s research is focused on Type IV pili, hairlike filaments that extend from the surfaces of many bacteria and mediate a diverse array of functions that are critical for bacterial colonization and dissemination and for acquisition of new genetic traits. The Craig lab applies an integrated approach of x-ray crystallography, cryo-electron microscopy, molecular modelling, biochemistry and genetics to understand Type IV pilus assembly, dynamics and functions in important human pathogens including Vibrio cholerae, enterotoxigenic E. coli, Pseudomonas aeruginosa and the pathogenic Neisseria. 

Title: Understanding Type IV pilus-mediated uptake and secretion 

Abstract: Type IV pili are long thin protein polymers present on many bacterial pathogens including Vibrio cholerae, enterotoxigenic E. coli and Neisseria gonorrhoeae. These filaments are critical virulence factors and attractive targets for vaccines and therapeutics. Type IV pili are both dynamic and adhesive, features that are key to their functions in host cell adherence, twitching motility, DNA and bacteriophage uptake, and secretion. Type IV pili rapidly extend across the cell wall, adhere to cell or abiotic surfaces or to substrates such as DNA or phage, then just as rapidly retract, pulling the bacteria close to or along the bound surface or pulling substrates into the cell. We have used x-ray crystallography and cryo-electron microscopy to decipher the molecular structure of the pilus and pilin subunits and to understand pilus assembly and retraction. We are now focused on the molecules located at the pilus tip, which is becoming recognized as the “business end” of the pilus. For this seminar I will describe our structural, biochemical and genetic data, which have provided a mechanistic understanding of Type IV pilus dynamics and functions with insights into how they might be exploited for antibacterial therapies.  

Albert Berghuis

McGill University



Dr. Berghuis is a Distinguished James McGill Professor in the Departments of Biochemistry and Microbiology & Immunology at McGill University, and the Associate Director of the McGill Antimicrobial Resistance Centre. His research focuses on exploiting various complementary biophysical techniques, such as X-ray diffraction/scattering and nuclear magnetic resonance spectroscopy, to examine protein-drug interactions in atomic detail. One of the research directions pursued by Dr. Berghuis is the structural elucidation of bacterial proteins that provide protection to antibiotics, thus conferring antimicrobial resistance. These studies have informed the development of next-generation antibiotics that are less susceptible to resistance, and the design of adjuvants that enhance the effectiveness of antibiotic therapies. In addition to his academic research, Dr. Berghuis serves on the editorial boards of several journals; he has consulted for the biotech and pharmaceutical industry; he has participated in and chaired expert panels advising granting agencies, such as CIHR, CFI and the US based NIH; and he has been a member of various advisory boards, including the Users’ Advisory Committee for the Canadian Light Source. 

Title: Antibiotic Resistance up close: a structural biology perspective on a global health treat 

Abstract: The dangers antibiotic resistance poses to human health needs little introduction. Statistics, such as that more than one million deaths annually are directly attributable to resistant bacteria, have been well publicized. The WHO has advocated a multi-pronged approach to address this global heath threat, which includes developing new medicines. We have used structural biological approaches to examine various mechanisms of antibiotic resistance, with the objective of informing the development of new therapeutic options. Notably,, we have examined enzyme-mediated resistance to aminoglycoside and macrolide antibiotics. Our findings have underscored the difficulties of drug development in the contexts of wide-spread multi-drug resistance, but have also revealed viable avenues to combat resistance. 


Rising Star: Justyna Fert-Bober

Cedars-Sinai Heart Institute



Dr. Fert-Bober is an Assistant Professor at Cedars-Sinai Heart Institute, with a broad background of biochemistry, molecular biology, immunology, and proteomics to study the changes that occur in the cell in response to exogenous factors. Her research involves inter-institutional collaborations focused on identifying novel and/or largely understudied biologic markers with the major role of proteins posttranslational modifications (PTMs).  PTMs are recognized as important mechanisms for subtle or dramatic alterations of protein function and provides a mean for cells to regulate diverse molecular processes. She is a pioneer in the understanding of peptidyarginine deiminases (PAD), family of five enzymes that introduce PTM, called citrullination. PAD-mediated citrullination, has been studied in different physiological and pathological conditions in the body. However, the role of PAD isoforms has not been fully studied in cardiovascular systemNeither, the pharmacological strategies for targeting PAD family proteins in cardiac diseases have not yet been studied. To fill this gap, her short-term goals are to concentrate on the experimental aspects of in vivo and in vitro studies related to the roles PAD isoforms in cardiovascular diseases including mechanisms, pathophysiological and therapeutic properties. Her second interest focus on an important role for citrullinated neoepitopes that induce robust autoimmune responses. The long-term goal is to  explore of anti-citrullinated autoantibodies combined with other multi-analyte “omic” profiles to form the basis of disease prediction allowing for earlier intervention linked to disease prevention strategies, as well as earlier, effective and personalized interventions for established disease.


Dr. Doug Muench

Department of Biological Sciences, University of Calgary


Sequence-specific RNA-binding proteins: structural and functional characteristics and potential for engineering RNA target specificity 

RNA-binding proteins (RBPs) have important roles in regulating the physiology of their RNA targets throughout the lifetime of the RNA, from processing in the nucleus to translation in the cytosol. Several classical RBP types exist, each having different mechanisms of binding to their RNA target. RBPs typically bind to a wide range of RNA targets, often recognizing RNA structure and sequence as well as interactions with regulatory proteins. However, some RBP types bind to their RNA targets with nucleotide sequence specificity. The PUF family of RBPs is widespread in eukaryotes and typically consists of eight tandem Puf repeats that each bind a single nucleotide in a one-repeat:one base manner. We identified an RNA target sequence of an Arabidopsis nucleolar PUF that is ten nucleotides in length, thereby increasing the sequence specificity of its binding to mRNA across the transcriptome. This RNA-binding domain represents a novel backbone that can be engineered and appended to functional domains to regulate specific mRNA targets in the cell. Recent RNA-interactome studies have also identified new types of RBPs, including those that ‘moonlight’ as RBPs on top of their primary role in the cell. We have identified a metabolic enzyme that possesses sequence-specific RNA-binding activity that may serve to regulate the activity of the enzyme or its synthesis through translational autoregulation. Although these two RBP types demonstrate sequence-specific binding, their mechanisms of binding are distinct.  

Dr. Andrew M. MacMillan

Department of Biochemistry, University of Alberta


Regulation of Gene Expression by the Protein Heart of the Spliceosome 

Splicing of precursor-messenger RNAs (pre-mRNAs) is an essential part of the maturation of protein-coding RNAs and is a key gene regulatory mechanism in all eukaryotic cells. Removal of pre-mRNA introns and ligation of exons is a two step process carried out by a complex RNA-protein assembly: the spliceosome. While the essential chemistry of splicing is RNA catalyzed, proteins regulate the fidelity and efficiency of splicing through orchestration of assembly and transitions within the spliceosome.  We are interested in the role of a large protein, PRP8, the most highly conserved nuclear protein in eukaryotes, found at the heart of the spliceosomal machinery. We have identified a regulatory switch found within PRP8 and are working to understand its role in the regulation of the spliceosomal mechanism. 

Dr. Ute Kothe

University of Lethbridge, Department of Chemistry & Biochemistry


Modifications in the T arm of tRNA globally determine tRNA function and cellular fitness

Sarah K. Schultz 1,2, Christopher D. Katanski 3, Richard Fahlman 4, Tao Pan 3, Ute Kothe * 1,2

1 Department of Chemistry, University of Manitoba, 144 Dysart Road, Winnipeg, R3T 2N2, MB, Canada

2 Alberta RNA Research and Training Institute (ARRTI), Department of Chemistry and Biochemistry, University of Lethbridge, 4401 University Drive, T1K 3M4 Lethbridge, AB, Canada

All tRNAs are highly modified and harbor 5-methyluridine at position 54 and pseudouridine at position 55 in the T arm, which are generated by the enzymes TrmA and TruB, respectively. Escherichia coli TrmA and TruB have both been shown to act as tRNA chaperones, and strains lacking trmA or truB are outcompeted by wildtype. Here, we investigate how TrmA and TruB contribute to cellular fitness. Deletion of trmA and truB in E. coli causes a global decrease in aminoacylation and alters other tRNA modification such as acp3U47 and 4-thiouridine. Whereas global protein synthesis is not significantly changed in DtrmA and DtruB, the expression of many specific proteins is altered at the translational level. In conclusion, we demonstrate that universal modifications of the tRNA T arm are critical for global tRNA function by enhancing other tRNA modifications, tRNA folding, tRNA aminoacylation, and translation of specific genes thereby improving cellular fitness and explaining their conservation.