Dr. Michael John Page completed his PhD studies at the CBR/BMB under Dr. Ross MacGillivray’s supervision. Michael had an endless excitement and drive for science, sports and life in general and he shared his passion and joy with his friends and colleagues. After his PhD, Michael went to the US where he was truly a rapidly rising star. Tragically, he died suddenly at the age of 36. Since that time, the CBR and the BMB honour his zest for life and science with a special annual award. This is open only to PDFs who are affiliated with the CBR and/or the Dept. of BMB. To receive this award is a great honour! The application details and form are attached. The deadline for submission is Friday, October 8, 2021. The successful applicant MUST be available to make a presentation at the award ceremony on Wednesday, October 27, 2021, via ZOOM at the weekly CBR seminar series time slot from 11 am to 12 noon.
Criteria:
This award is open to Postdoctoral Fellows in the Department of Biochemistry & Molecular Biology or the Centre for Blood Research in recognition of outstanding academic achievement combined with significant extra-curricular achievements (both scientific and non-scientific). Nominees must have held a PDF appointment at UBC for at least 1 year.
Deadline:
Please complete all documentation and send to Mira Milutinovic (mira.milutinovic@ubc.ca)by 4:30pm on Friday, October 8, 2021.
Title: “Understanding the diversity, biochemistry, and biological role of endo-glucanase 16 enzymes in the context of plant evolution”
Hila Behar, Dr. Brumer Lab, University of British Columbia
Abstract: The plant cell walls are dynamic structures that are mainly composed of polysaccharide components. Hence, the synthesis, maintenance, and modification of the cell walls are carried out by carbohydrate active-enzymes (CAZymes). The highly conserved members of endo-glucanase 16 (EG16) are CAZymes identified as distinct from the widely studied cell wall modifying enzymes xyloglucan endotransglycosylase/hydrolase (XTH), based on their substrate specificity and structural differences. While XTH gene products catalyze the rearrangement and cleavage of xyloglucan, a cell wall glycan, EG16 gene products exhibit a broad substrate specificity and hydrolyze the hemicelluloses mixed-linkage β-glucan (MLG), xyloglucan, and soluble cellulosic substrates. A census of the publicly available genome and transcriptomes showed that EG16 orthologs were found in all plant clades spanning nearly 500 million years of evolution. Notably, the observation of EG16 orthologs in the charophyte green algae species that are the most phylogenetically distant from land plants, supports that EG16-like genes are ancestors to extant EG16 and XTH genes. Further biochemical investigation of EG16 orthologs from the distantly related moss, Physcomitrella patens, and a woody poplar species showed that their substrate specificities, primary hydrolysis site, and digest products are conserved. Correspondingly, elucidation of the biological role of EG16 in the species above, shows that they display similar gene expression patterns in young tissues as well as leaderless cell wall localization. However, in P. patens, EG16 gene deletion yielded larger plants that senesced earlier than wild-type, whereas, in poplar, gene downregulation did not affect growth. This research serves as a foundation for the study of the EG16 clade members and informs their evolutionary history, conserved activity, cell wall localization, and involvement in growth.
Hosted by Dr. Harry Brumer
Title: “Optimization of Lipid Nanoparticles containing Small Molecule Drugs and Genetic Drugs”
Nisha Chander, Dr. Cullis Lab, University of British Columbia
Abstract: Lipid-based nanoparticle (LNP) drug delivery vehicles can be used for in vivo delivery of a variety of bioactive molecules including nucleic acid polymers and small molecule drugs for applications ranging from improving the efficacy of anticancer drugs to enabling gene therapies. However, two major problems remain. First, while liposomal LNP systems containing small molecule drugs such as anticancer drugs can be designed to be relatively non-toxic and long-circulating, the ability to trigger rapid release of drug cargo at the target site remains elusive. This severely limits the improvement in therapeutic index that can be gained by liposomal delivery. The second problem concerns systems containing genetic drugs such as RNA-based drugs. Currently, intravenous administration only results in effective gene silencing or gene expression in the liver. This thesis has two major objectives. The first objective is to develop lipid nanoparticles that are capable of releasing a larger payload at the target site to improve their overall efficacy.
The first two research chapters of this thesis focus on incorporating photoswitchable lipids or metal nanoparticles into previously well-established liposomes with the objective of developing systems that could be responsive to externally applied radiation such as laser light or radiofrequency irradiation to trigger drug release. There have been many attempts to develop triggered release systems for liposomal systems containing anticancer drugs that leak contents in response to local heating or irradiation. Despite more than 30 years of experimentation, these efforts have failed to result in clinically approved applications. This is due to the fact that many of the systems are complex and/or exhibit poor drug loading/retention and relatively short circulation lifetimes resulting in off-target release and reduced ability to access the desired target tissues. Ideally, new systems for light-triggered release should closely mimic the composition and properties of clinically approved LNPs in terms of composition, size, loading, and stability. The first two research chapters of this thesis include the development of modified LNP or liposomal systems that have similar size and drug encapsulation properties as parent systems, while also exhibiting triggered release properties.
The third research chapter of this dissertation describes an attempt to develop transfection competent long circulation systems that can transfect extra-hepatic tissues following intravenous administration. The approach taken is to increase the proportion of so-called “helper” lipids in LNP formulations of mRNA. It is shown that high (40 mol%) levels of helper lipids such as egg sphingomyelin (ESM) can result in improved gene expression both in vitro and in vivo, particularly in extrahepatic tissues such as bone marrow. This ability is attributed to the unique morphology of these LNP systems which exhibit a “solid” hydrophobic core surrounded by a lipid bilayer. Such systems allow improved distribution to extrahepatic tissues due to an enhanced circulation lifetime.
Hosted by Dr. Pieter Cullis
Monday, September 13, 2021 at 2:30 pm. Join by Zoom.
Congratulations Charles! On July 5th, 2021 Haoran Charles Li successfully defended his thesis, “Investigating molecular clustering of Rv1747 in M.smegmatis”. Charles was a trainee in Dr. Joerg Gsponer’s Lab.
Congratulations Rose! On June 4th, 2021 Rose Zhou successfully defended her thesis, “Investigating the in vitro and in vivo anti-resorptive effects of herbal-and TCM-based extracts on Cathepsin K activity.” Rose was a trainee in Dr. Dieter Bromme’s Lab.
An international team led by UBC researchers has used proteomics to map how proteins interact, revealing how the same protein, expressed in two different tissues, can have dramatically different impacts.
Dr. Nicollas Scott
“These findings have significantly advanced the understanding of how the same set of protein “parts” can be differently arranged in cells across tissues,” says first author Dr. Nicollas Scott, a former UBC fellow who now heads a laboratory at the Doherty Institute in Melbourne, Australia.
“This is a major advance for basic science, but also in our understanding of human disease,” says senior author Dr. Leonard Foster, a professor in UBC’s Department of Biochemistry and Molecular Biology. “Many inherited diseases are caused by a genetic mutation that is present in every cell in the body, but causes dysfunction in only one tissue.”
In humans and other life forms, proteins are encoded by the genome and interact with one another to perform normal cellular functions. “Proteins are like parts and although there is only a limited number of different types of parts in a given cell, how these can be put together in organizations known as protein complexes, can be quite different,” explains first author Michael Skinnider, a UBC MD/PhD student based in Dr. Foster’s lab at the LSI.
In the two decades since the human genome was first sequenced, vast amounts of money have been poured into mapping complete protein-protein interaction networks in humans and other model organisms.
Dr. Leonard Foster
Up until now, most insights into protein interaction networks have been gained using cell culture-based systems, but these do not always mirror what is observed within tissues.
“As a result, their relevance to physiological contexts like living tissues has never been truly clear,” states senior author Dr. Jörg Gsponer, associate professor in UBC’s Department of Biochemistry and Molecular Biology. For example, inherited cardiac myopathies cause problems in the heart, but not the liver or the thymus. Understanding the differences that exist between different tissues in the human body will help clarify why certain diseases occur in one organ and not another.”
“By characterizing how the protein complexes of tissues are put together, this can help us explain the functionality differences between tissues and why disease associated proteins can have certain impacts in one tissue over another,” adds Scott.
“Using these findings, we have generated a resource for the community so that people can look at what each protein interacts with in different tissues to gain new insights into different disease models and better understand how a given protein works in their authentic states,” said Skinnider.
These protein-protein interaction maps were built using a novel technique called protein correlation profiling, which enabled the team to take protein complexes isolated from mouse tissues, separate them using size exclusion chromatography, then monitor which proteins are found together. Then by using computational approaches and the concept of ‘guilt by association’ the team reconstructed the protein interaction networks in each tissue.
Dr. Jörg Gsponer
“Being able to use tissues to explore interaction networks enables us to get a better picture of how proteins are interacting with each other in a way which is a lot closer to what is actually happening in our own bodies,” highlights Scott.
“Understanding the molecular organization of all the different cells in the different tissues in the human body has been, and is of central interest to many branches of life science,” reflects Foster. “As has so often been the case, technological developments from our labs enabled us to take on this challenge.” (Kristensen et al., Nature Methods 2012).
Over the past decade, the researchers have refined and adapted both the wet-lab techniques as well as the sophisticated computational tools that are required to make sense of the huge amount of data their technique generates. “However, bringing the assay into in vivo mice was a major technological leap that occurred in this study for the first time, and allowed us to take a major step forward towards understanding proteins and their interactions in physiological contexts,” says Gsponer.
“Our hope is that this will be a high-quality resource to be used by thousands of research groups around the world,” adds Skinnider. “This is the first data where we have been able to directly measure the interaction network in different tissues, as opposed to just predicting what turned out to be low quality networks.”
Michael Skinnider
The research team plans to continue to develop the technology, and are currently applying it to study, among other things, how the interaction network in honey bees responds to infection, and how the interaction network in human cells responds to a coronavirus, such as SARS-CoV-2.
Read the paper: Skinnider M.A., Scott, N.E., Prudova, A. , Craig H. Kerr, C.H., Stoynov, N., Stacey, R.G. et al. (2021) An atlas of protein-protein interactions across mouse tissues DOI: 10.1016/j.cell.2021.06.003.
