The focus of the Mar lab is to understand how variability in gene expression contributes to the regulation
of cellular phenotypes.
Not exact matches
The objective
of the research project led by Marko Kallio, Principal Scientist at VTT, was to accelerate the drug development process by identifying new compounds that would possess similar binding properties and
cellular phenotype, but a different chemical structure, as the selected drugs in clinical use or investigational compounds in development.
Using this approach, researchers can easily generate diseaserelevant isogenic models to determine the impact
of correcting or introducing disease - relevant mutations on
cellular phenotypes in a tissue - appropriate context.
He also envisions that this kind
of nanomechanical
phenotyping should allow for the development
of predictive models for
cellular behavior for any kind
of cell.
Environmental factors interact with the different subgenomes to modify the transcription
of their component genes and to modulate the translation
of protein products and their posttranslational modification, yielding changes in protein and
cellular function and metabolism, and defining an intermediate
phenotype.
This series addresses the contribution
of cellular senescence to cardiovascular, neurodegenerative, and arthritic disorders as well as the senescent
phenotypes in various tissues and cell types.
Often this garners more compelling evidence
of a gene's importance, because it demonstrates the relationship between a genetic entity and
phenotype visible at the
cellular level or above.
In order to dissect these defects, we utilize a unique approach including deep assessment
of patient
phenotype, clinical genetic testing to identify underlying genetic contributions to these features, and the application
of combinatorial functional omics (transcriptome, metabolome, etc.) to uncover the pathological
cellular states that result from these genetic changes.
The ability to isolate pure CSC populations using
cellular markers has led to advances in our understanding
of the heterogeneity and plasticity
of the CSC
phenotype.
Here, Anna presents how studies
of neural stem cells and neurons derived from iPS cells
of patients show faithful mimicking
of known disease
phenotypes in our
cellular models
of disease, like Alzheimer's disease, autism, and Down syndrome.
RNAi - mediated silencing
of RASSF1A induced epithelial - to - mesenchymal transition (EMT), fomenting a motile and invasive
cellular phenotype in vitro and increased metastatic prowess in vivo.
The consequences
of gene extinction on DM1
phenotype is then monitored at the molecular level by quantitative PCR or at the
cellular level by high content screening in 96 or 384 - well plate format.
Employing a combination
of cellular, biochemical and genetic experiments, we showed that (i) human and murine pericytes express functional Tie2 receptor, (ii) Tie2 - silenced pericytes have a pro-migratory
phenotype, (iii) Tie2 downstream signalling in pericytes involves Calpain, Akt and FOXO3A, (iv) Ng2 - Cre - driven deletion
of pericyte - expressed Tie2 delays developmental angiogenesis and vessel maturation, and (v) Tie2 deletion in pericytes results in a pro-angiogenic tumour vasculature with enhanced tumour growth.
Current explorations into the molecular underpinnings
of cell circuitry are leveraging multiple data types including expression profiling and epigenetic analysis leveraging RNA - seq and CHiP - Seq coupled with molecular markers and
cellular phenotypes.
The apparent temporally identical and phenotypically opposing tumour vessel
phenotypes may relate to the
cellular findings
of the present study, in which the pericyte Tie2 loss -
of - function
phenotype phenocopied the Ang2 gain
of function.
She has discovered several novel disease specific
cellular phenotypes in their in vitro models, many
of them involved in accurate performance
of the neural progenitors.
(9) Indeed, the degenerative aging process is by definition one in which the organism progressively accumulates damage to its
cellular and molecular components over time, so any genetic or environmental factor that leads to a greater burden
of such damage will bear some resemblance to the aging
phenotype, irrespective
of the causal origin
of the defect or its relationship to «normal» aging.
The SMDC has allowed Gladstone scientists to design molecules to modulate the functions
of proteins or specific
cellular phenotypes and, most significantly, screen for drugs that could be used as therapies for disease.
The routine use
of MSC
cellular therapy with would benefit from a uniform cell source, with stable
phenotype and function as well as providing a solution to potential safety issues.
By expanding high - throughput deep
phenotyping of cells beyond protein epitopes to include RNA expression, PLAYR opens a new avenue for the characterization
of cellular metabolism.
Therefore, this work provides strong support for the use
of iPSC ‐ derived MSC as a more uniform with well ‐ defined
phenotype and function as a sustainable source
of cells which paves the way for a clinical application for IBD
cellular therapy.
To define the
phenotype and function
of specific
cellular populations involved in the cross-talk between cancer and immune cells we make use
of both flow - cytometry and mass - cytometry.
These data indicate that
cellular senescence is causally implicated in generating age - related
phenotypes and that removal
of senescent cells can prevent or delay tissue dysfunction and extend healthspan.
Only in the last 10 years, with increasing knowledge
of the senescent
phenotype and the ability to detect senescent cells in human tissues, have biologists been able to investigate the relationship between
cellular senescence and disease.
This lack
of understanding is contributed by the fact that
cellular aging is a complex
phenotype to measure and comprehensive studies on aging require the application
of novel experimental approaches and technological platforms.
Genome - wide CRISPR - based knockout (CRISPR - KO) screening is an emerging technique which enables systematic genetic analysis
of a
cellular or molecular
phenotype in question.
Through genome - wide profiling we find that 5 - 46 %
of the variation in different iPS cell
phenotypes, including differentiation capacity and
cellular morphology, arises from differences between individuals.
Children suffering from autism have been reported to have low bone mineral density and increased risk for fracture, yet the
cellular origin
of the bone
phenotype remains unknown.
Other flow cytometry applications include:
cellular phenotyping by multiparameter cytofluorimetric analysis, sorting
of fluorescence protein - tagged cells, assessing apoptosis and cell cycle status, the identification / isolation
of stem and cancer stem cells (e.g., marker positive, side - population, etc.) and the deposition
of single cells.
This study therefore characterizes the structural and
cellular bone
phenotype in a mouse model
of autism that can be further utilized to investigate therapeutic avenues to treat bone fractures in children with autism.