Best Biochemistry Lab Winnipeg Near Me

4worldlovers: We are interested in understanding how the different fragments of a gene are selectively combined (spliced) to produce multiple products in biology and diseases. This process has profound implications in the evolution and functional complexity of genes/gene products. Its disruption is a major consequence of the mutations that cause human genetic diseases. Our research has focused on the molecular basis of adaptive splicing, likely involved in cell adaptation, neuron homeostasis and neurological diseases. This has also allowed us to discover a novel class of introns (REPAG-harboring) contributing to the evolution of alternative splicing, gene product diversity or the aberrant splicing in diseases. Particularly welcome to join us are students with backgrounds in biochemistry, genetics, computer science or statistics.

Alternative splicing is a common way of gene regulation that allows the generation of multiple mRNA and often protein isoforms from a single gene. Almost all human gene transcripts are alternatively spliced and some are known to generate extremely diverse protein isoforms. This greatly contributes to the proteomic complexity, particularly in neurons and endocrine cells. In experimental animals, genetic deficiencies in alternative splicing factors result in developmental defects or embryonic-lethal phenotypes. In humans, aberrant splicing accounts for the defect of at least 30% of genetic mutations that cause diseases. Thus, it is imperative to understand alternative splicing and its regulation in biology and diseases in the omics era.

For example, in electrically excitable cells such as neurons, endocrine and muscle cells, ion channels allow ions in/out of the cell membranes to generate electrical firing patterns that are important for cell functions including memory, hormone secretion and muscle contraction. These processes are believed to be critical for higher order phenotypes such as learning, behavior, metabolism and heart beating. How these processes are finely tuned during development and in adult life is still a mystery to researchers. Alternative splicing provides a unique way to diversify proteins and may play a critical role here. A number of studies have indicated that alternative splicing is involved in adaptive or addictive changes in neurons by neuronal activity or alcohol stimulation.

Interestingly, alternative splicing of some ion channel genes is regulated by membrane depolarization, the first part of an action potential, implying a gene expression change related to the electrophysiological memory observed in neurons, or hormone production in response to experience in life (e.g. exercise or stress). However, the molecular basis of the splicing regulation, particularly after recurrent stimulation, remains largely unclear.

We have used the STREX (stress axis-regulated exon) variant of the Slo1BK potassium channel gene as a model to study how cell signals regulate the choice of alternative splice sites in pre-mRNA transcripts. Inclusion of the STREX exon enhances the calcium sensitivity of BK channels and likely modulates cellular electrical properties related to hearing frequency tuning or adaptive changes in learning and memory or tolerance to alcohol. Its regulation by stress hormones and the calcium/calmodulin-dependent protein kinase IV (CaMK IV) makes it an interesting target for dissecting the components regulating alternative splicing as well as understanding the impact of splicing regulation on neuronal electrical properties. A first step toward this goal was made by coupling CaMK IV with a pre-mRNA element (CaRRE1) sufficient to confer CaMK IV response to an otherwise non-responsive exon. We have recently identified the splicing factors hnRNP L and L-Like (LL) as essential components of the CaMKIV-regulated splicing of STREX by inhibiting U2AF65 binding to the upstream 3' splice site. Particularly for hnRNP L, its Ser513 is phosphorylated and essential for the regulation.(Fig. 1) Other factors including PTB and hnRNP K are involved in the regulation as well.

In particular, hnRNP L and LL are required for the differential regulation and protection of the hormone gene expression programs for producing prolactin and growth hormones. Further detailed characterization of this molecular process and its role in adaptive hormone production and stress response is ongoing.

4worldlovers:
Physicians and other practitioners, to whom we provide screening and diagnostic information derived from laboratory analysis.

Manitoba Health staff in support of disease control programs, e.g. sexually transmitted disease and Environmental Health.

Medical Officers of Health, Public Health Inspectors, Public Health Nurses, for whom we assist in investigating outbreaks and cases of public health significance.

Other laboratories, who use CPL as a referral centre for special tests.

The University of Manitoba, for which we provide teaching and research opportunities.

Investigators and researchers, who we assist as collaborators in Public Health studies, investigations or research projects.

Students, associates and others who benefit from our consultation, training and research functions.