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Tag Archives: Dalhousie University

Friday Science Review: March 4, 2011

The Origin of Meier-Gorlin Syndrome

Dalhousie University ♦ University of Montreal ♦ University of British Columbia

Published in Nature Genetics, Feb. 27, 2011

Researchers have mapped a locus for Meier-Gorlin syndrome (MGS), a rare genetic condition characterized by short stature, small ears, and reduced or absent kneecaps. A mutation in the ORC4 gene seems to be at the root of the disorder. ORC4 is a component of the eukaryotic origin recognition complex.

To map the locus responsible for MGS researchers performed high density genome-wide SNP genotyping using a panel of 600,000 markers provided by Illumina. The next stop involved PLINK, a whole genome analysis toolset, which was able to identify a haplotype on chromosome 2 within a number of affected individuals. Sequencing of coding exons located in the ORC4 gene led to the identification of a missense mutation that causes a tyrosine (residue 174) to cysteine switch in the ORC4 protein. The tyrosine residue affected in MGS is completely conserved across eukaryotes suggesting it has an important function; the amino acid is also believed to interact with a conserved arginine residue on a nearby helix motif in the protein structure. In the absence of this interaction the structural integrity of the protein could be compromised in part.

The origin recognition complex consists of six proteins in humans and is essential for DNA replication. It plays a critical role in recognizing origin sites on DNA and in the formation of DNA replication forks. This is the first report of an inherited mutation in any gene of the origin recognition complex in the vertebrate literature.

The Human Serum Metabolome

University of Alberta ♦ National Institute of Nanotechnology

Published in PLoS ONE, Feb. 16, 2011

Human biofluids are very important from a clinical standpoint given the insight they can provide into the disease conditions of a human being. The study of metabolomics attempts to identify, on a large scale, the composition of metabolites found in these biofluids. The advent of advanced analytical techniques along with mounting pressures for scientists in the metabolomics community to document the entire human metabolome, led to the development of the Human Metabolome Project. The project is supported by Genome Alberta and Genome Canada, the latter of which is a private, non-profit, corporation that received $600 million in funding from the Canadian government to develop and implement a national strategy in genomics and proteomics.

The most recent contribution to the project is a comprehensive multicentre study led by Dr. David Wishart at the University of Alberta. Using a diversity of metabolomics platforms researchers were able to identify, and quantify, metabolites found in human serum. The use of different methods, including nuclear magnetic resonance (NMR), and various mass-spectrometry platforms (GC-MS, LC-MS), increased the overall coverage of the serum metabolome. Data gathered via these platforms was linked to computer-aided literature mining which allowed for the development of a virtually complete set of metabolites. In total the group found 4,229 metabolites, but this number may increase in coming years as more powerful characterization techniques are developed.

Dr. Wishart and his colleagues previously characterized the human cerebrospinal fluid metabolome.


Friday Science Review: January 14, 2011

The Eukaryotic Tree of Life Expands

Dalhousie University ♦ Published in PNAS, Jan. 4, 2011

Photosynthetic marine organisms carry out roughly half of the primary production on the planet today. Tracing the lineages of these tiny creatures has helped us document eukaryotic evolution and draw conclusions on the events that led to their current distribution and the distribution of the genetic content hidden within them. A new lineage of photosynthetic algae, being referred to as rappemonads, has been discovered by Dr. John Archibald’s lab group in the Department of Biochemistry and Molecular Biology at Dalhousie University. Phylogenetic analysis using operons from plastid ribosomal DNA indicates that this new group is indeed evolutionarily distinct. Furthermore, scientists revealed that the habitat distribution of rappemonads is wide; environmental DNA sequencing in the North Atlantic, North Pacific, and at European fresh water sites suggests an extensive diversity. Although flare-ups of this new species are rare, they are believed to be able to form transient blooms. Quantitative PCR analysis was able to detect large quantities of rappemonads rRNA in the Sargasso Sea. Discoveries of this nature bring to mind the Sorcerer II expedition — launched by Craig Venter in 2004 — where researchers traveled the world’s oceans to discover new microbial species. The field of environmental genomics is in its infancy, and has the potential to help us alleviate some of our environmental issues and elucidate many aspects of biodiversity and evolution.

Novel Vaccine Delivery Formulation Protects Against Respiratory Pathogen Challenge

Institute for Biological Sciences, NRCC ♦ Published in PLoS ONE, Dec. 29, 2011

Mucosal surfaces represent an excellent opportunity for microbial pathogens to invade the body and give rise to infections. Currently many systemic vaccines targeting these pathogens fail to elicit adequate mucosal immunity in the host. It is for these reasons that Dr. Wangxue Chen and his colleagues at the NRCC are developing mucosal vaccines that specifically target these entry points. Creating long lasting and memory boostable immune responses has proven difficult with mucosal vaccines however, and they typically require an adjuvant, or delivery vehicle, to be successful.  The team at NRCC has found that intranasal immunization of mice with a cell free extract of Fransicella tularensis has much more pronounced effects when it is paired with archael lipid mucosal vaccine adjuvant and delivery (AMVAD). The technology incorporates cell free extract, from the organism against which immunity is desired, into liposomes which can then be delivered as a vaccine. Mice receiving the AMVAD/extract preparation had lower pathogen burden in the lungs and spleen, longer mean time to death, and significantly greater overall survival than mice that received just the cell free extract or naive mice receiving no vaccination.

Oxidative Stress of Surrogate Tissues Mirrors that of the Prostate

McMaster University ♦ University of Toronto ♦ Published in PLoS ONE, Dec. 28, 2011

Researchers believe that surrogate androgen regulated tissues from the same host can be used to determine the oxidative stress (OS) status of the prostate. Androgens have long been known to drive the formation of prostate cancer. Oxidative stress is regulated by androgens, so reducing OS is a key target in the prevention of prostate cancer. Using a mouse model researchers show that the level of prostatic OS is correlated with the OS of Dermal Papillary Cells, a cell type found in hair follicles, and also the salivary glands – two exocrine glands that express the androgen receptor and are morphologically similar to the prostate. Determining the OS status of the prostate and patient response to prevention strategies directly, would require taking a biopsy sample from the prostate itself. Thus, the findings of Dr. Jehonathan Pinthus and his team at McMaster University could have great implications for the non-invasive and indirect evaluation of prostate OS status and patient response to prevention strategies.

Monday Biotech Deal Review: November 29, 2010



Welcome to your Monday Biotech Deal Review.  I hope our American readers had a very happy thanksgiving weekend, but hopefully there’s still some room left for your weekly digest of biotech deals.  This week witnessed the closing of the US$52M IMRIS financing [Ed. -- as well as a rafter of other deals].  Read on to learn more about these and other deals from the previous week.  Read more of this post

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