Our students have chosen Abigail Chapman to be our newest Zbarsky recipient.
The SH Zbarsky Scholarship is awarded to an outstanding PhD student in the Department of Biochemistry and Molecular Biology. The scholarship has been endowed by the friends and colleagues of Dr. SH Zbarsky in recognition of his outstanding contributions to Biochemistry and UBC. Dr. Zbarsky was one of the original two members of the UBC Department of Biochemistry, when it was established in 1950. Each year, the Zbarsky Scholarship is given to a 3rd year Biochemistry PhD grad, who presented the best BIOC 530 seminar. The successful candidate is voted by their peers. For 2021W the Zbarsky Award has increased to $3,200.
“Title: Biochemical and Structural Characterization of the Elongator, TINTIN and PI3K Gamma Complexes”
Abstract: In eukaryotes, protein complexes are often composed of catalytic enzymes along with non-catalytic subunits that can modulate the stability, interaction patterns, and activities of the catalytic subunits. In this thesis, three such complexes are biochemically and structurally characterized to uncover how their activities are regulated: the the tRNA modifying Elongator complex, the transcription associated TINTIN complex, and the lipid kinase PI3Kg complex.
Conserved from yeast to humans and composed of six subunits (Elp1 – Elp6), Elongator catalyzes the modification of the anticodon loop of transfer RNAs (tRNAs) and in turn regulates messenger RNA (mRNA) decoding efficiency. How the different human Elongator subunits coordinate with one another to catalyze tRNA modification are not fully understood. By examining human Elongator and its subunits by single-particle electron microscopy (EM), co-purification and pulldown assays, and substrate binding assays, we found that the complex shares similar overall morphologies as the yeast counterparts, and the accessory proteins serve to stabilize ELP3 and improve the binding of substrate tRNAs.
The heterotrimeric TINTIN complex is an important regulator of transcriptional elongation. Composed of the Eaf3, Eaf5, and Eaf7 proteins, TINTIN exists as both as a module within the NuA4 histone acetyltransferase complex as well as independently. TINTIN is targeted to chromatin through Eaf3, a chromodomain-containing protein that is shared with the Rpd3S histone deacetylase complex. A combination of co-immunoprecipitation and hydrogen deuterium exchange mass spectrometry (HDX-MS) revealed that upon binding Eaf5 and Eaf7, Eaf3 undergoes conformational changes which improves the affinity of Eaf3 towards nucleosomes trimethylated at Lys 36 of histone H3 (H3K36me3). Negative stain single-particle electron microscopy (EM) analysis of TINTIN in complex with nucleosomes revealed that TINTIN binds to the disc edge of nucleosomes with increased specificity in the presence of H3K36me3. Together, this work provides molecular insights into the dynamics of TINTIN and the mechanism by which its interactions with chromatin are regulated.
The class IB phosphoinositide 3-kinase (PI3K), PI3Kγ, is a master regulator of immune cell function and a promising drug target for both cancer and inflammatory diseases. Critical to PI3Kγ function is the association of the p110γ catalytic subunit to either a p101 or p84 regulatory subunit, which mediates activation by G protein–coupled receptors. The cryo–electron microscopy structure of p110γ-p101 reveals the novel architecture of the p101 regulatory subunit and demonstrates a unique assembly that is distinct from other class I PI3K complexes.
Monday, November 22, 2021 at 2:30 pm at LSC #3 and or join by Zoom.
A honey bee queen is the sole egg-layer in a colony, and colony fitness depends on her health and productivity. Worryingly, beekeeper surveys show that “poor queen quality” is one of the most frequently reported causes of colony death, but little is known about the underlying cause of declining quality. I research biotic and abiotic factors affecting queen fertility, with a focus on temperature stress, which has become even more relevant in the wake of the heatwave last June. In this talk, I’ll describe how queens are vulnerable to temperature stress, practical methods of mitigating risk, and implications this stress response has on queens’ ability to combat infectious disease.
About Michael John Page Postdoctoral Fellow Award
The Michael John Page Postdoctoral Fellow Award recognizes a Postdoctoral Fellow who reflects Dr. Page’s academic excellence and his passion for life.
Dr. Michael John Page
Michael John Page was born and raised in Thunder Bay, Ontario where he graduated from the Port Arthur Collegiate in 1994. Mike then attended Carleton University in Ottawa graduating with his B.Sc. degree in biochemistry in 1998. Mike entered the UBC Biochemistry & Molecular Biology graduate program under Ross MacGillivray’s supervision and supported by competitive graduate studentships from Canadian Blood Services. During his time in the MacGillivray lab, Mike designed, created and hosted the first web site for the UBC Centre for Blood Research. Mike successfully defended his Ph.D. thesis entitled Bioengineering coagulation factor Xa substrate specificity into Streptomyces griseus trypsin in 2004. During his graduate studies, his fellow graduate students recognized Mike’s achievements by selecting him for the 2001 Zbarsky Prize. Dr. Page then completed a highly productive postdoctoral fellowship studying the biological activity of thrombin with Dr. Enrico Di Cera at Washington University in St. Louis. In 2010, Mike moved to a junior faculty position at the University of California, San Francisco supported by a grant from the American Heart Association and mentored by Dr. Charles Craik. At UCSF, Michael developed a peptide-based probe that was able to detect blood clots in real time. He and his team won a major biochemical entrepreneurship competition that also stimulated him to patent his discovery and to form a spin-off company called Biopaint Inc. Tragically, Mike collapsed and died suddenly in June 2013 at age 36. In addition to Mike’s sustained academic success, he was well-liked by his peers and friends. As one colleague describes him:
Mike was the essential glue in keeping our group coherent during grad school and made those years so memorable for all of us.
After his arrival in Vancouver in 1998, Mike hosted the annual biochemistry hockey tournament in Vancouver and whether in Vancouver, St. Louis or San Francisco, he continued to host the tournament and to maintain his support for his beloved Vancouver Canucks hockey team. Mike was always there to help and support his colleagues. Mike was a great guy who was fun to be around – he really had a passion for life. As one of his graduate student colleagues recalls:
Mike had an endless excitement and drive for science, sports and life in general and he shared all of those interests with his friends
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The Astell Award is to recognize trainees at all levels in Biochemistry and Molecular Biology at UBC for outstanding commitment to activities related to promoting Equity, Diversity, and Inclusion (EDI).
The Astell Award was name after Dr. Caroline Astell one of the first women faculty in Biochemistry and Molecular Biology at UBC. Dr. Astell completed her undergraduate degree in Math/Zoology, Masters in Genetics and PhD in Biochemistry/Nucleic Acids all at UBC. After completing a postdoctoral fellowship at Rockefeller University in the USA, she worked at the University of Toronto as a Research Associate and then as an Assistant Professor at the University of Calgary. She then returned to UBC as a Research Associate and advanced through the ranks to Assistant, Associate and full Professor in Biochemistry and Molecular Biology. Dr. Astell’s research focused on understating the molecular biology of animal viruses and the structure and replication of eukaryotic chromosomes. She had both an impressive funding and publication track record, leading to over 62 published papers, numerous book chapters and patents and a co-authored book on Nobel Laureate Michael Smith. Dr. Astell was also a dedicated member of the department, leading many committees and the BC Genome Sciences Center. She was also an avid instructor in Biochemistry and directly mentored 11 graduate students and served on over 40 student supervisory committees during her career. Dr. Astell retired from UBC in 2004 and continues to serve her local community through volunteer and outreach activities.
“The tangled history of mRNA vaccines,” a news feature published today in Nature, reflects on the culmination of work by hundreds of scientists who worked on mRNA vaccines for decades before the coronavirus pandemic brought a breakthrough.Former LSI Director Pieter Cullis is featured for his linchpin contributions in lipid nanoparticles (LNPs). “Many experts highlight another innovation that was crucial for mRNA vaccines — one that has nothing to do with the mRNA,” writes science journalist Elie Dolgin. “It is the tiny fat bubbles known as lipid nanoparticles, or LNPs, that protect the mRNA and shuttle it into cells.
“This technology comes from the laboratory of Pieter Cullis, a biochemist at the University of British Columbia in Vancouver, Canada, and several companies that he founded or led. Beginning in the late 1990s, they pioneered LNPs for delivering strands of nucleic acids that silence gene activity. One such treatment, patisiran, is now approved for a rare inherited disease.”
Title: Self-amplifying RNA: The Next Generation of RNA Vaccine Technology
Dr. Anna Blakney, Assistant Professor, University of British Columbia
Abstract: Self-amplifying RNA (saRNA) is a next-generation platform for nucleic acid vaccines. The backbone, typically derived from an alphaviral genome, encodes a gene of interest (GOI) and a replicase, which is able to amplify the RNA upon delivery to the cell. The self-amplification properties enable use of a much lower dose of saRNA compared to messenger RNA (mRNA), typically 100-fold lower. Because RNA is a large, anionic molecule, it requires a delivery vehicle to promote cellular uptake and protect it from degradation. Lipid nanoparticle (LNP) formulations are the most clinically progressed technology for both saRNA and mRNA delivery, with the recent approval of the Pfizer/BioNTech and Moderna COVID-19 vaccines, which are both LNP formulations. However, there are other delivery systems in development, such as polymeric nanoparticles, and there are still many unknowns as to the role of the delivery vehicle in vaccine immunogenicity. Here, we will discuss development of an saRNA COVID vaccine, alternative delivery systems and the future of RNA platform technology.
Monday, September 20, 2021 at 2:30 pm LSC #3or join by Zoom
