Research Focus Teams
COVID-19, Cancer, Rare Disease, Cardiovascular, Diabetes, Tuberculosis
Research Interests
Infectious diseases, Proteomics
Departments
Biochemistry & Molecular Biology
Bio
Dr. Leonard Foster is Professor and Head of the Department of Biochemistry and Molecular Biology at the University of British Columbia (UBC). Dr. Foster grew up in northern BC and earned his B.Sc at SFU in 1996. He moved to Toronto to complete a doctoral degree in the cell biology and biochemistry of insulin's effects on adipocytes. From there he went to the University of Southern Denmark to study mass spectrometry and proteomics with Matthias Mann. In 2005 he took up his current position at UBC. Dr. Foster's group at UBC develops and applies quantitative proteomic methods to study host-pathogen interactions in a variety of systems.
Research Summary
Host-pathogen interactions:
mammalian-bacterial, honeybee-bacterial, honeybee-mite.
Our lab is focused on quantitative proteomics using LC-ESI-MS to study biological systems. We cover a wide range of topics including pathogen invasion, infection, protein localization, and mapping protein interaction.
Mass spectrometry-based proteomics:
In order to understand how a complex system works it is extremely useful to know the identities of as many of the components of the system as possible. Commercially available mass spectrometers and database search tools have advanced to the point where experienced laboratories can routinely and reliably identify hundreds or thousands of proteins in exceedingly complex mixtures (i.e. an organelle preparation) using nanoflow high performance liquid chromatography (HPLC)/tandem mass spectrometry (LC/MS). Typically, complex protein samples are reduced to peptides by highly specific enzymatic digestion (e.g. trypsin cleavage carboxy-terminal of Arg or Lys). The peptides are then resolved by extremely high-resolution reversed-phase chromatography and eluted/ionized directly into a mass spectrometer (MS). The MS, operating in an information-dependent mode, selects and isolates any peptide ions observed and subjects them to tandem mass spectrometry. The observed mass/charge ratio of the peptide and its fragmentation pattern are then used to scan comprehensive protein sequence libraries (e.g. for a human liver sample the data would be searched against the Homo sapiens library) to find the best theoretical match and the peptides are compiled to arrive at a ΓÇÿprotein hit list'.
In the past few years we have witnessed great advances in methodologies for applying mass spectrometry-based proteomics to answer biologically relevant questions. Some of the most powerful of these methods involve the use of stable isotopes to incorporate a quantitative dimension into the experiment. Thus far, however, quantitative proteomics has yet to be widely applied in mainstream biology. Our group is interested in a multidisciplinary approach to relevant cell biological problems. We develop and apply quantitative proteomic methods to questions involving organelles and how the composition of these compartments change when antagonized. Additionally, we are involved in several projects involving host-pathogen interactions. The knowledge gained from proteomic experiments is then used to direct more in-depth biochemical, bioinformatic and cell biological analysis of the system in order to validate the proteomic results. We have an LTQ-Orbitrap and an LTQ-FT in our laboratory, both equipped with autosamplers and nESI-interfaced HPLCs.
Ongoing Projects
Current Projects:
- Finding host targets of effector proteins secreted from pathogenic bacteria
- Protein interaction network mapping of methicillin-resistant S. aureus (part of the PRoteomics for Emerging Pathogen REsponse
- Exploring why young honeybee larvae are susceptible to invading bacteria, especially to Paenibacillus larvae , the causative agent of American Foulbrood.
- Exploring the dynamic composition of lipid rafts
- Host signal transduction cascades initiated by pathogens
- Host receptors for pathogenic bacteria
- Development of software tools to improve the acquisition, analysis, storage and dissemination of proteomic data
Recent Publications
Leishmania regulates host YY1: Comparative proteomic analysis identifies infection modulated YY1 dependent proteins
Defining enteric bacterial pathogenesis using organoids: Citrobacter rodentium uses EspC, an atypical mucinolytic protease, to penetrate mouse colonic mucus
Optimizing imputation strategies for mass spectrometry-based proteomics considering intensity and missing value rates
Western red cedar (Thuja plicata) beehives have no impact on honey bee (Apis mellifera) overwintering colony survival or detoxification enzyme expression
Multimodal cell maps as a foundation for structural and functional genomics
Honey bee egg composition changes seasonally and after acute maternal virus infection
Pyruvate dehydrogenase kinase 1 controls triacylglycerol hydrolysis in cardiomyocytes
Protein bL38 facilitates incorporation of uL6 during assembly of the 50S subunit in Flavobacterium johnsoniae
Factors affecting heat resilience of drone honey bees (Apis mellifera) and their sperm
Role of the sarcin-ricin loop of 23S rRNA in biogenesis of the 50S ribosomal subunit
Preclinical assessment of splicing modulation therapy for ABCA4 variant c.768G>T in Stargardt disease
Regional patterns and climatic predictors of viruses in honey bee (Apis mellifera) colonies over time
Transfection Potency of Lipid Nanoparticles Containing mRNA Depends on Relative Loading Levels
Bile acid-induced metabolic changes in the colon promote Enterobacteriaceae expansion and associate with dysbiosis in Crohn's disease
Immunoproteomic discovery of Mycobacterium bovis antigens, including the surface lipoprotein Mpt83 as a T cell antigen useful for vaccine development.
Identifying and modeling the impact of neonicotinoid exposure on honey bee colony profit
Genetic engineering of megakaryocytes from blood progenitor cells using mRNA lipid nanoparticles.
HumanIslets.com: Improving accessibility, integration, and usability of human research islet data.
Differences in honeybee queen pheromones revealed by LC-MS/MS: Reassessing the honest signal hypothesis
Phosphate availability conditions caspofungin tolerance, capsule attachment and titan cell formation in Cryptococcus neoformans.
Beta-hydroxybutyrate promotes basal insulin secretion while decreasing glucagon secretion in mouse and human islets
Glutathione-mediated redox regulation in Cryptococcus neoformans impacts virulence
Proteomic predictors of individualized nutrient-specific insulin secretion in health and disease
What proteomics has taught us about honey bee (Apis mellifera) health and disease
Higher prevalence of sacbrood virus in Apis mellifera (Hymenoptera: Apidae) colonies after pollinating highbush blueberries
Development of automated proteomic workflows utilizing silicon-based coupling agents
Sex-Based Mechanisms of Cardiac Development and Function: Applications for Induced-Pluripotent Stem Cell Derived-Cardiomyocytes
Characterization of Argonaute-containing protein complexes in Leishmania-infected human macrophages
Pivotal functions and impact of long con-coding RNAs on cellular processes and genome integrity
Honey bee stressor networks are complex and dependent on crop and region
Mechanisms of pathogen and pesticide resistance in honey bees
Global interactome mapping reveals pro-tumorigenic interactions of NF-κB in breast cancer
Oral infectivity through carnivorism in murine model of Trypanosoma cruzi infection
Investigating trade-offs between ovary activation and immune protein expression in bumble bee (Bombus impatiens) workers and queens
A murine model of maternal micronutrient deficiencies and gut inflammatory host-microbe interactions in the offspring
Metagenomic analysis of the honey bee queen microbiome reveals low bacterial diversity and Caudoviricetes phages
Mapping protein states and interactions across the tree of life with co-fractionation mass spectrometry
Deep Learning-Enabled MS/MS Spectrum Prediction Facilitates Automated Identification Of Novel Psychoactive Substances
Leishmania infection upregulates and engages host macrophage Argonaute 1, and system-wide proteomics reveals Argonaute 1-dependent host response
Identification of Emerging Novel Psychoactive Substances by Retrospective Analysis of Population-Scale Mass Spectrometry Data Sets
British Columbia beekeeping revenues and costs: survey data and profit modeling
Indirect exposure to insect growth disruptors affects honey bee (Apis mellifera) reproductive behaviors and ovarian protein expression
Recent advances in targeting the "undruggable" proteins: from drug discovery to clinical trials
Cleavage of 14-3-3ε by the enteroviral 3C protease dampens RIG-I-mediated antiviral signaling
Truncated TDP-43 proteoforms diagnostic of frontotemporal dementia with TDP-43 pathology
Small-molecule dual inhibitors targeting heat shock protein 90 for cancer targeted therapy
Discovering Protein-Protein Interactions using Co-Fractionation-Mass Spectrometry with Label-Free Quantitation
Targeting bromodomain-containing proteins: research advances of drug discovery
Integration of data-independent acquisition (DIA) with co-fractionation mass spectrometry (CF-MS) to enhance interactome mapping capabilities
Breaking spore dormancy in budding yeast transforms the cytoplasm and the solubility of the proteome
The Effects of Helicobacter pylori-Derived Outer Membrane Vesicles on Hepatic Stellate Cell Activation and Liver Fibrosis In Vitro
A Multipronged Unbiased Strategy Guides the Development of an Anti-EGFR/EPHA2-Bispecific Antibody for Combination Cancer Therapy
CRISPR-induced DNA reorganization for multiplexed nucleic acid detection
Ribosomes lacking bS21 gain function to regulate protein synthesis in Flavobacterium johnsoniae
Synaptic activity-dependent changes in the hippocampal palmitoylome
Fertility costs of cryptic viral infections in a model social insect
Impact of Azo Dyes and Ibuprofen on the Proteome of Serratia nematodiphila sp
The adult mouse proteome
Development of a Method Combining Peptidiscs and Proteomics to Identify, Stabilize, and Purify a Detergent-Sensitive Membrane Protein Assembly
Review of the Real and Sometimes Hidden Costs in Proteomics Experimental Workflows
Where protein structure and cell diversity meet
Thermal Proteome Profiling Reveals the O-GlcNAc-Dependent Meltome
Drone honey bees are disproportionately sensitive to abiotic stressors despite expressing high levels of stress response proteins
Proteomic Profiles of Staphylococcus aureus Strains Associated with Subclinical Bovine Mastitis
Phenomic analysis of the honey bee pathogen-web and its dynamics on colony productivity, health and social immunity behaviors
Proteomic analysis of metabolic pathways supports chloroplast-mitochondria cross-talk in a Cu-limited diatom
Bicyclic Picomolar OGA Inhibitors Enable Chemoproteomic Mapping of Its Endogenous Post-translational Modifications