The Cross-Border Biotech Blog

Biotechnology, Health and Business in Canada, the United States and Worldwide

Tag Archives: transcription factor

Friday Science Review: March 26, 2010

Why Did the Duck Kill the Chicken? Well… a scientific explanation is RIG-I.  Ducks are resistant to influenza viruses but may by asymptomatic carriers.  One of the reasons for ducks’ resistance is because ducks express the RIG-I protein that senses the presence of the viruses.  Chickens, however, do not appear to express RIG-I or a similar protein and have no method to detect the presence of viruses to illicit an immune response.  This could have implications to the poultry industry who do not want to see their entire farm wiped out by a viral outbreak and may want to start breeding transgenic chickens expressing RIG-I.  The discovery was led by Dr. Katharine Magor and her team at the University of Alberta and is published in the early edition of the Proceedings of the National Academy of Sciences.

Promoting Cancer Cell Growth: The YB-1 (Y-box binding protein-1) transcription factor is a known oncogene that is expressed in a significant percentage of breast cancers.  In this study, scientists demonstrated that YB-1 induces the expression of CD44 and CD49f, which are associated with cancer stem cells and used as stem cell markers.  Although they do not make a direct link to breast cancer stem cells, they suggest that it is this link that explains why YB-1 expressing cancers are resistant to drugs such as paclitaxel and are associated with disease recurrence and poor outcome.  The principal investigator of the study was Dr. Sandra Dunn at the University of British Columbia. Details of the study were reported in Cancer Research.

Knock, knock… Let Me In: A transporter protein that is selectively expressed in blood cells can be manipulated to facilitate the entry of cancer drugs into the cell.  This is extremely important for new treatment regimes against blood cancers such as AML and other leukemias.  Researchers found that the Human Carnitine Transporter encoded by the SLC22A16 gene acts as a gateway and can mediate the uptake of the polyamine class of drugs such as the anti-cancer agent Bleomycin.  Dr. Dindial Ramotar, Université de Montréal, first demonstrated this in yeast cells and now in human cells as reported in the Journal of Biological Chemistry.

Please, No More Radiation: A genetic mutation in the p53 gene in children with a rare type of brain cancer – choroid plexus carcinoma (CPC) – is a new marker indicating a poor response to radiation therapy.  It is unfortunate that this signals a more aggressive disease, however, this finding would relieve the patient of having to suffer through the difficulties of radiation.  The inherited p53 mutation is associated with a condition called Li-Fraumeni syndrome and is found in about 50% of CPC cases.  Without the mutation, CPC patients treated by radiation have a good chance of recovery.  The study, led by Dr. David Malkin at the Hospital for Sick Children, Toronto, is published in the advance online issue of the Journal of Clinical Oncology.

Mooooooooo: Scientists have finished sequencing the genome of two different types of cows – one beef and one dairy – using Life Technologies’ next generation SOLiD™ 3 System.  It cost $130K and took only seven months to complete.  In comparison, it cost $50M and four years, finishing in 2009, to sequence the first cow.  The genomic information is important to the industry for making breeding decisions and to identify genetic markers of specific desirable traits.  So that T-bone steak waiting for you to grill up this summer will be even juicier and tastier.  The Bovine Genomics Program at the University of Alberta led by Dr. Stephen Moore performed the sequencing study.

Bookmark and Share

Friday Science Review: March 5, 2010

Missing Enzyme Improves Metabolism: Mice lacking the TGH gene for the enzyme triacylglycerol hydrolase showed an unexpected dramatic improvement in their metabolic profile.  TGH is an enzyme that helps to release stored fat or triglycerides into the blood stream where it circulates to be used as an energy source or, if in excess, ends up being stored at tissue sites that do not normally store fat depots.  This contributes to cardiovascular diseases, diabetes, and liver dysfunction.  Researchers were correct in hypothesizing that deleting TGH would prevent this from happening but they were surprised to discover global metabolic benefits.  These mice not only have better lipid profiles but they also burn more fat and are also more physically active compared to mice that have the enzyme.  Additional research is required but this study demonstrates the potential of TGH as a therapeutic target for lowering blood lipid levels and likely other related benefits in humans.  The study was led Dr. Richard Lehner and his team at the University of Alberta and is published in this month’s issue of Cell Metabolism.

Gene Duplication Causes Bleeding Disorder: The genetic cause of the rare blood clotting disorder, Quebec Platelet Disorder (QPD) was recently discovered by researchers at McMaster University.  QPD is caused by a mutation involving an extra copy of the gene encoding the enzyme urokinase plasminogen activator (uPA), resulting in an overproduction of the enzyme that accelerates blood clot breakdown.  This transforms blood platelets from clot forming to clot busters.   A genetic test for the mutation, the first gene duplication mutation causing a bleeding disorder, is in development and will be an invaluable diagnostic tool.  Dr. Catherine Hayward led the discovery team and their study is published in the journal Blood.

Blocking Metabolic Genes: Prox1 is the newest player in the control of our body’s energy balance.  It binds to and inhibits two well known transcription factors for metabolic genes, estrogen-related receptor alpha (ERRalpha) and proliferator-activated receptor gamma coactivator-1alpha (PGC-1alpha).  These are significant findings along the long road to understanding the complex regulation and homeostasis of our metabolic system.  Dr. Vincent Giguère and his team at McGill University’s new Goodman Cancer Centre describe their work in the latest issue of Genes and Development.

Molecular Clues to Chemotherapy Resistance: Scientists at The Campbell Family Institute for Breast Cancer Research knocked out a specific isoform of the p73 protein family, DeltaNp73, to try to delineate the specific function of this protein.  They discovered a novel function whereby the DeltaNp73 protein targets the DNA damage site and partners with another protein, 53BP1, to block the subsequent DNA damage molecular response pathway involving p53.  This has significance in explaining chemotherapy resistance in human tumors with high levels of DeltaNp73 expression.  Dr. Tak Mak reports the study in Genes and Development.

Friday Science Review: December 18, 2009

Advancing Cell Research with Proteomic Tools: Advances in technology – particularly in proteomics – are allowing scientists to perform research in more complex systems, a complexity that more closely reflects the situation inside the body.  In the latest trend, researchers can label two different populations of cells with different modified amino acids and use mass spectrometry to distinguish proteins derived from one population versus the other.  This strategy was recently applied to study the EphB2 receptor protein, which plays an important role in a cell’s communication with an adjacent cell expressing ephrin-B1 protein.  Differential labeling allowed the researchers to determine the unique (and similar) molecular signaling network in each cell population as they coordinate their self-organizational activity.  It’s a powerful tool that can be adapted to investigate various systems that cannot be studied in isolation.  The research was performed in Dr. Anthony Pawson’s group at the Samuel Lunenfeld Research Institute and is published in the journal Science.

New Member in the Protein Synthesis Club: After decades of studying and trying to fully understand the mRNA translational machinery for protein synthesis, new components in this complex process continue to be discovered.  The latest is a protein called DHX29, a helicase enzyme that helps to untangle the nucleic acid during the initiation phase of translation.  Down-regulating the enzyme holds up protein synthesis and presents a possible target point to block cancer cells from growing.  Indeed, when the researchers blocked DHX29 in cancer cells, tumour growth was significantly reduced.  Dr. Nahum Sonenberg was the lead author of the study reported in the early online edition of the Proceedings of the National Academy of Sciences.

PS.  Congratulations to Dr. Sonenberg in becoming the 2009 Researcher of the Year for Biomedical and Clinical Research presented by CIHR.

Low Oxygen Response in Cancer Cells:  Within a large tumour, there may be areas of hypoxic microenvironments – regions that are under low oxygen conditions.  Cells in this environment undergo a stress response to try to adapt by carrying out a process called autophagy.  The consequence of this is that the cancer cells ‘get tough’ and subsequently become resistant to radiation therapy.  This recent study investigated one of the possible cell adaptation methods through activation of the unfolded protein response (UPR) pathway.  Induction of two key proteins, MAP1LC3B and PERK, were required for autophagy.  They also demonstrated that inhibition of autophagy resulted in the cells becoming sensitive to hypoxia and irradiation.  Thus, the molecular players involved in autophagy may be good therapeutic targets.  Dr. Bradly Wouters at the Ontario Cancer Institute led the research and reports the findings in the Journal of Clinical Investigation.

Teasing out the Role of E2f Transcription Factors: Members of the E2f family of transcription factors are key regulators that commit cells through the cell division process.  Information in the literature is somewhat perplexing regarding whether they are essential for this process and different studies will support one argument or the other.  New research settles this debate – at least for the E2f1-3 isoform.  Through a series of expression and deletion studies and looking at the different molecular players involved, it was concluded that E2fs are not absolutely required for normal cell division.  The surprise finding is that E2f1-3 is necessary for cell survival in development and its function switches from ‘activator’ in progenitor cells to ‘repressor’ mode in differentiating cells.  The research was conducted at Toronto Western Research Institute by Dr. Rod Bremner’s team and appears in this week’s Nature journal.  The story is corroborated in another similar study in the same issue.

Possible Risk for Diabetes or Heart Disease: A large genome-wide study revealed an association between a polymorphism in the ARL15 gene (ADP-ribosylation factor-like 15) with lower levels adiponectin.  Adiponectin is a fat cell protein and its circulating level is inversely associated with type 2 diabetes and coronary heart disease.  Accordingly, the polymorphism is also associated to some degree with higher risk of heart disease, diabetes and other metabolic related traits.  Surely this requires a more in depth molecular study but this is a good example of how you can sift through large amounts of data from various genome-wide studies and fish out an important finding.  Dr. Brent Richards, now at McGill University, is the corresponding author of the study published in PLoS Genetics.

Genetic Mutation in Intellectual Disability: Approximately 50% of intellectual disability cases are not related to other syndromes.  In these cases, an explanation for the intellectual disability may lie in the gene called TRAPPC9, where a mutation in the gene causes a truncated form of the protein and renders it inactive.  The research team led by Dr. John Vincent at the Centre for Addiction and Mental Health used microarrays to screen a family that had seven members with non-syndromic intellectual disability to map the TRAPPC9 gene.  Additional families with mutations affecting the same gene validated the importance of TRAPPC9, which encodes proteins involved in the NF-κB signaling pathway.  With this new knowledge, researchers can screen patients or family members to track the mutation and also dig deeper into the mechanisms in the brain that affects cognitive development.  The study appears in the American Journal of Human Genetics.

Follow

Get every new post delivered to your Inbox.

Join 126 other followers