Posted on March 9, 2022
Title: More ubiquitins than meets the eye: Novel variants encoded by ubiquitin pseudogenes.
Professor, Department of Immunology and Cell Biology. Director of the Cancer Research Institute of the Universite de Sherbrooke. Faculty of Medicine and Health Sciences.
Abstract: Post-translational modification by ubiquitin and ubiquitin-like modifier proteins regulate cellular processes at almost every levels. Ubiquitin itself is encoded by four different genes: the UBA52 and RPS27A genes code for a single copy of ubiquitin fused to the ribosomal proteins L40 and S27A, respectively, and UBB and UBC genes code for polyubiquitin precursors. Early studies identified several additional genes potentially coding for ubiquitin, but they were considered pseudogenes due to differences in amino acids compared to ubiquitin. Through analysis of large-scale proteomics and RNA sequencing experiments, we found evidence for expression at the mRNA and protein levels of several of the ubiquitin pseudogenes. Our results show that UBBP4, a pseudogene of the UBB subfamily, produces functional ubiquitin proteins with slightly different amino acids composition compared to the canonical sequence, and includes additional lysines. These ubiquitins variants are covalently conjugated to proteins that are different from ubiquitin, and proteins modified by UBBP4 are not targeted for proteasomal degradation. Interestingly, we have identified different protein targets including proteins involved in DNA replication and cell cycle progression when comparing UBBP4 with the canonical ubiquitin, demonstrating a specificity in the choice of protein substrates, and suggesting a different role for these novel ubiquitin variants. This implies that a subset of E3 ligases can specifically recognize these ubiquitin variants, and underlines the fact that some of the reported ubiquitin targets could rather be through these variants arising from wrongly annotated pseudogenes. Moreover, knockout of UBBP4 through CRISPR/Cas9 results in reduced cell growth and mislocalization of nuclear proteins. The identification of additional ubiquitin variants thus entails a new layer of complexity in protein regulation by ubiquitylation that has been unnoticed until now.
Monday, March 21, 2022 at 2:30 pm at LSC 3 and Zoom
Hosted by: Dr. Leonard Foster
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Posted on February 18, 2022
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Posted on February 8, 2022
Laura Andrews – EDI Support
Laura Andrews is a Research Technician in the Gross Anatomy Lab. She also provides Admin Support for the CPS REDI Committee, BMB EDI Committee and CPS Seminar Series. She is responsible for facilitating the body donation process in the lab, helping with REDI Committee initiatives, taking meeting minutes for both committee meetings and organizing upcoming seminars. Laura has a strong academic background in anatomy, physiology, and dissection. Outside of work you can find her rock climbing, skiing, or hiking with her 1-year-old Australian Shepherd mix!
You can find Laura in our admin office on Tuesday and Wednesday afternoons.
Contact: laura.andrews@ubc.ca
Euri Park – Program Assistant
Euri Park is a Program Assistant for Department of Biochemistry & Molecular Biology and Cellular & Physiological Sciences.Euri brings a unique presence to the department, with their administrative experience that spans variety of different fields, including construction and communications. In their spare time, Euri croquets and water paints and they aspire to live peacefully with a cat.
Euri’s responsibility includes;
- Process appointments for graduate, undergraduate and Work Learn students
- Collect, track and submit student work hours
- Post exam marks on Faculty Service Centre
- Copy and scan undergraduate exams and generate reports using Scantron
- Book classrooms for all department offered courses
- Assist course coordinators with CANVAS for undergraduate courses
- Maintain office supplies inventory
- Sort and route mail/faxes/courier packages
You can find Euri in our admin office on Monday, Thursday and Friday.
Contact: euri.park@ubc.ca
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Posted on February 4, 2022
UBC faculty of medicine researchers are leading 48 projects that were recently funded through the Canadian Institutes of Health Research (CIHR) Project Grants: Fall 2021 competition, including our department’s faculty members, Drs. Seth Parker and Natalie Strynadka.
The CIHR Project Grants Fall 2021 competition approved 417 research grants, plus 1 bridge grant, for a total investment of approximately $325 million. In addition, 105 priority announcement grants were funded for a total amount of $12,292,500 and 13 supplemental prizes were awarded for a total of $400,000.
In total, UBC researchers are leading 48 projects awarded Project Grants totalling $34.7 million. A further 13 UBC-led projects were awarded priority announcement grants totalling $1.3 million.
Principal Investigator: Dr. Seth Parker
Metabolism is like a recipe book and metabolites are the ingredients that our cells use to grow and function. If our cells become cancerous, they use different recipes to grow which also affects what ingredients are needed. If we can understand which ingredients are required by cancer cells and what they use these ingredients for, then we might be able to design therapies that can slow or stop cancer growth. We study amino acids, a set of metabolites that are important building blocks for making proteins but also can provide the cell with energy and other molecules. Pancreatic cancers, which is a very deadly cancer with very few effective therapies, have a significant appetite for certain amino acids, like alanine, and become dependent on transporters that bring alanine into cancer cells for growth. Alanine can be used to make proteins, other amino acids, DNA and RNA, and fat as well as energy. In this research project, we aim to understand which recipes pancreatic cancer cells use alanine for and why they become dependent on alanine transporters for growth, which might provide insight into new treatments for this deadly disease.
Structure-guided in vitro and in situ analysis of virulence linked secretion systems in drug-resistant bacteria
Principal Investigator: Dr. Natalie Strynadka
Bacteria have evolved sophisticated assemblies to passage macromolecules essential to subsequent disease across their lipid membrane barriers. The Type III Secretion system “injectisome” is one prominent example, a syringe like complex that is essential for downstream pathogenesis of many health elated bacterial species in the clinic and community. This includes the causative agents of food and water borne disease, plague, hospital acquired infections, sexually transmitted disease and beyond. A remarkably sophisticated complex of two dozen highly oligomerized proteins spanning the 2 membranes of the bacteria as well as that of the human host cells they infect, the Strynadka laboratory has been a leader in the structure-guided study of the molecular underpinnings of how the injectisome works. Here her laboratory proposes to use a combination of sophisticated biophysical tools including xray crystallography and cryogenic electron microscopy (single particle/tomography) supported by cellular microbiology to study the atomic features and function of the injectisome in isolation and within the native context of the bacterial cells whose pathogenicity they promote. A related but distinct nanomachine, with many analogies to the Type III injectisome, is the “feeding tube” apparatus Clostridioides difficile mother cells use to passage essential molecules to the daughter cell, the latter which is destined to become a robust long-lived spore that allows this notorious hospital acquired pathogen to persist under even the harshest sanitization methods. The Strynadka laboratory propose to use a similar toolbox of biophysical and microbiology methods to study this fascinating system in vitro and in situ within C.difficile cells. Atomic information gleaned from these studies will drive essential understanding of how molecules are passaged across multiple membranes, and sets the foundation for design of antimicrobials to block their action and subsequent disease causing effects.
Find the original post on the Faculty of Medicine website.
A full list of Priority Announcement Grant Recipients is available on the CIHR website.
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Posted on January 20, 2022
Title: Structural basis for the DASS/SLC13 family’s carboxylate transport, chemical inhibition, and pathogenesis
Dr. David Sauer, P.I of Membrane Protein Structural and Chemical Biology, Centre for Medicines Discovery, University of Oxford.
Abstract: Citrate, α-ketoglutarate, and succinate are TCA cycle intermediates that also play essential roles in metabolic signalling and cellular regulation. These molecules are imported across the plasma membrane by the divalent anion sodium symporter (DASS) protein family, encoded by the SLC13 genes in humans. Underlining their biomedical importance, mutations in NaDC3 (SLC13A3) and NaCT (SLC13A5) result in neurological disorders. We determined several structures of two bacterial DASS proteins, including the previously unseen outward-facing state, to provide biophysical descriptions of the family’s elevator transport mechanism and strict substrate coupling. Building from this, we determined structures of the human citrate transporter NaCT in complexes with citrate or a small-molecule inhibitor. These revealed how the inhibitor arrests the transport cycle of NaCT, and explains compound selectivity. Together, the bacterial and NaCT structures provide a framework for understanding how various mutations abolish the transport activity and thereby cause SLC13A5-Epilepsy.
Monday, January 31, 2022 at 2:30 pm via Zoom
Hosted by: Dr. Seth Parker
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Posted on January 6, 2022
The Biochemistry & Molecular Biology (BMB) department is proud to introduce a new mentorship program that will be piloted this upcoming term. The program will match mentors and mentees within BMB to build meaningful connections with a professional, career, and scientific focus.
This program is open to all members of the BMB department (Undergrads, Grad students, post-Docs, PI’s) and will be running from Jan-Apr 2022. This initiative aims to foster a sense of community within the BMB program with an emphasis on Equity, Diversity, and Inclusion.
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Posted on December 29, 2021
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