The phenotyping department of PHENOMIN - ICS is advancing a technical platform for functional characterization of preclinical
models of human diseases with respect to both genetic understanding of pathophysiological mechanisms and the assessment of drug therapies.
Not exact matches
These findings allowed researchers to create a chimera virus: a mouse virus
with a
human viral gene that can be used to test molecules that inhibit
human LANA protein in an animal
model of disease, treating not only
human herpes virus infection but also its associated cancers.
With our
human gut - on - a-chip, we can not only culture the normal gut microbiome for extended times, but we can also analyze contributions
of pathogens, immune cells, and vascular and lymphatic endothelium, as well as
model specific
diseases to understand complex pathophysiological responses
of the intestinal tract.»
Even the new studies clashed somewhat: Unlike the UCSF study, the German research found no major differences between the overall microbiomes
of twins
with and without MS. Finally, mouse
models of MS are not perfect mimics
of the
human disease, and mouse immune systems aren't identical to people's.
«The study results elucidate the molecular mechanisms underlying
disease progression in multiple sclerosis
models, providing a basis for future clinical trials to determine safety and efficacy
of these chemical agents in
humans with demyelinating disorders,» says Patrizia Casaccia, MD, PhD, Professor
of Neuroscience, Genetics and Genomic Sciences at Mount Sinai and senior author
of the study.
«Computational
models like this one might one day be able to predict the clinical course
of a
disease or injury, as well as make it possible to do less expensive testing
of experimental drugs and interventions to see whether they are worth pursuing
with human trials,» he said.
These techniques include:
human tissue created by reprogramming cells from people
with the relevant
disease (dubbed «patient in a dish»); «body on a chip» devices, where
human tissue samples on a silicon chip are linked by a circulating blood substitute; many computer
modelling approaches, such as virtual organs, virtual patients and virtual clinical trials; and microdosing studies, where tiny doses
of drugs given to volunteers allow scientists to study their metabolism in
humans, safely and
with unsurpassed accuracy.
«While it seems that genetics makes a substantial difference to the severity
of the heart
disease in our
models, it does suggest that in
humans we may be able to better diagnose heart valve
disease in people
with rheumatoid arthritis in the future.»
Desgrosellier said the team will follow up
with mouse
models containing tumor fragments from patients to better reflect the diversity
of cell types present in
human disease.
Most animal studies
of the
disease are conducted
with laboratory mice that have been genetically engineered and bred to
model ALS, but for this research, investigators used rats
with ALS because they more accurately portray the
disease's variable course in
humans.
With that in mind, the Penn Vet team chose to examine two
of their well - established canine
models of RP, which recapitulate many features
of the
human diseases, each involving mutations in different genes.
But if homologous recombination could be worked out in
human (embryonic) stem cells, then cardiomyocytes
with mutations in ion channels could be derived, as well as a large number
of other very useful
disease models of other tissues.
The monkey
model has its own limitations: Monkeys don't develop severe
disease when infected
with different serotypes
of dengue virus, which clearly happens in
humans.
Grima used two mouse
models of Huntington's
disease: one
with a
human version
of the mutant Huntingtin protein and another
with an aggressive form
of the
disease that contains only the first portion
of the mouse Huntingtin protein.
Using a
model of Parkinson's
disease in which the toxin MPTP, made famous in book «The Case
of the Frozen Addicts,» induces Parkinson's - like symptoms in
humans and mice, Dr. Smeyne showed that mice infected
with H1N1, even long after the initial infection, had more severe Parkinson's symptoms than those who had not been infected
with the flu.
The phosphorylation
of eIF2alpha, which decreases protein synthesis, was previously found at elevated levels in both
humans diagnosed
with Alzheimer's and in Alzheimer's
Disease (AD)
model mice.
It's now possible to not only
model disease using the cells, but also to compare iPSCs from
humans to those
of our closest living relatives --- great apes,
with which we share a majority
of genes --- for insight into what molecular and cellular features make us
human.
In recent years, researchers have found that both
humans with Alzheimer's
Disease and AD
model mice have relatively high levels
of eIF2alpha phosphorylation.
«We use zebrafish to study Alagille syndrome because these vertebrates allow us to use experimental approaches that aren't possible
with other
disease models,» says Duc Dong, Ph.D., assistant professor in the
Human Genetics Program at SBP and senior author
of the paper.
Having shared the environment
with humans ever since its appearance, the dog has been exposed to similar pathogens, and therefore represents an important
model system for the study
of human diseases.
-- 90 percent
of genes associated
with disease are identical in the
human and the mouse, supporting the use
of mice as
model organisms.
The only way to do that, he reasoned, was to go beyond individual experiments
with behaviors,
diseases and brain anatomy and instead
model the circuitry
of the entire
human brain.
The researchers» strategy — generating
disease - specific nerve cells, identifying a causative gene for developmental defects, validating the gene - specific defect in animal
models, and then investigating interactions
with other genes both in animal
models and in
humans — represents a promising new approach for understanding the mechanisms underlying some
of the most intractable psychiatric illnesses.
The similarity
of the mouse and
human genetic make - up means that genes associated
with disease in
humans can be studied and further investigated in mouse
models.
Investigating mouse
models for biological for research The congress aims to promote the International Mouse Phenotyping Consortium (IMPC) mouse lines, importance
of mouse phenotyping & clinical and drug discovery collaboration, to present progresses performed by IMPC
with regards CRISPR editing genome, rare
diseases, microbiota and ageing pipeline, as well as illustration
of examples
of scientific projects about «Animal
models for
human diseases» and recent developments in mouse
models phenotyping imaging.
«What we've shown in the monkey
model matches a lot
of what people have observed in epidemiological studies
of humans,» says Emma Mohr, a pediatric infectious
disease fellow at UW — Madison and first author on the study
with Matthew Aliota and Dawn Dudley, research scientists in UW — Madison's schools
of Veterinary Medicine and Medicine and Public Health, respectively.
The Center, which collaborates
with CiRA, is creating
human, iPS - based
disease models needed to accelerate drug development for a host
of devastating for cardiovascular, viral and neurological illnesses.
FOA encourages research grant applications from institutions / organizations that propose to develop, characterize or improve animal
models for
human disease or to improve diagnosis and control
of diseases that might interfere
with animal use for biomedical research purposes.
Molecular mechanism underlying
diseases (conformational
diseases, cystic kidney disorders, neuromuscular
diseases, inflammation, iron - related
diseases, disorders
of human reproduction, osteoporosis and bone
diseases) are being investigated by many groups
with robust animal and cellular
models and patients» biological samples.
NYSCF partners
with a broad range
of institutions, foundations, centers and companies in a variety
of ways ranging from the creation
of fundamental research resources such as iPSC lines for a
disease area to developing
human disease models in vitro to enable drug discovery and toxicity testing.
With the reference cell census data in hand, the research team is excited to conduct additional studies, including ones involving models or human patients with gastrointestinal conditions — Crohn's disease, ulcerative colitis, gastrointestinal cancers, forms of food allergy, etc. — aimed at identifying changes in gene expression and epithelial structure and function that could reveal new insights and opportunities for therapeutic developm
With the reference cell census data in hand, the research team is excited to conduct additional studies, including ones involving
models or
human patients
with gastrointestinal conditions — Crohn's disease, ulcerative colitis, gastrointestinal cancers, forms of food allergy, etc. — aimed at identifying changes in gene expression and epithelial structure and function that could reveal new insights and opportunities for therapeutic developm
with gastrointestinal conditions — Crohn's
disease, ulcerative colitis, gastrointestinal cancers, forms
of food allergy, etc. — aimed at identifying changes in gene expression and epithelial structure and function that could reveal new insights and opportunities for therapeutic development.
Jason Heaney, Baylor College
of Medicine -
Modelling human disease variants in murine ortholog (s)
with CRISPR / Cas9
The authors say their next step will be to introduce gut bacteria from IBD patients into the mouse
model with the goal
of identifying pathobiont species that drive
human disease.
In recent years, researchers have developed so - called «senolytic» drugs that wipe out senescent cells in aging mice and mouse
models of age - related
disease, exploiting the high dependence
of these cells on specific biochemical survival pathways.9, 10 In these studies, senolytic drugs have restored exercise capacity9 and formation
of new blood and immune precursor cells11 in aging mice to near youthful norms, and prevented or treated mouse
models of diseases of aging like osteoarthritis, 12 fibrotic lung
disease, 13 hair loss, 14 atherosclerosis, 15,16 and age - related
diseases of the heart itself.9 UNITY Biotechnology is leading a growing charge toward the clinic,
with human clinical trials expected to begin in 2019.
Telomere length predicts both cellular health and
disease in rodent
models and
humans.8 Shorter telomeres predict onset
of cardiometabolic
diseases of aging.9 Chronic stress is associated
with higher inflammation, shorter telomeres, and lower activity levels
of telomerase, the cellular enzyme that elongates telomeric DNA.10, 11 Levels
of amyloid beta (Aβ) proteins circulating in the blood appear to be stress - related in rodent
models12 and may be affected by stress reduction, and greater Aβ42 / Aβ40 ratios are associated
with lower risk
of dementia.13
His lab develops isogenic
human pluripotent stem cells and transgenic animals to
model disease,
with the goal
of delineating novel approaches to influence outcomes for Huntington
disease (HD) and Fragile X Syndrome (FXS), the most common genetic causes
of dementia and intellectual disability, respectively.
Each month through partnerships
with researchers around the world, the MMRRC enhances critical research
with a continuously expanding catalog
of mouse
models of human disease.
Using genetic and epigenetic analyses coupled
with powerful perturbation technologies to test gene functions in
human cells and mouse
models, we hope to identify the critical drivers
of this
disease and the basis for therapeutic responses.
For such study, we have used the McGill - R - Thy1 - APP transgenic rat, which is unique compared to other rodent
models in that the AD - like phenotype has been achieved
with a single genomic insertion
of a mutated
human APP transgene; minimizing off - target genetic corruption and therefore being closer to the
human disease [32].
Moreover, PHENONIM - ICS is involved in European projects presenting a strong impact on
human health: Interreg CARDIOGENE (Genetic mechanisms
of cardiovascular
diseases), GENCODYS (Genetic and epigenetic networks involved in cognitive dysfunctions), AgedBrainSYSBIO (Basic studies
of brain aging), as well as projects in partnership
with industry: MAGenTA (an Industrial Strategic Innovation project supported by Bpifrance about the treatment
of major urogenital
diseases) and CanPathPro (H2020 program), to develop a predictive
modeling platform
of signaling pathways involved in cancers.
The congress aims to promote the International Mouse Phenotyping Consortium (IMPC) mouse lines, importance
of mouse phenotyping & clinical and drug discovery collaboration, to present progresses performed by IMPC
with regards CRISPR editing genome, rare
diseases, microbiota and ageing pipeline, as well as illustration
of examples
of scientific projects about «Animal
models for
human diseases» and recent developments in mouse
models phenotyping imaging.
To build upon the encouraging early discoveries, Helmsley renewed and expanded its Crohn's funding for the Institute in 2013 to begin new work
with three major aims: 1) continue studies
of individual genes to determine how genetic differences between Crohn's patients and healthy individuals contribute to the
disease; 2) evaluate promising small molecules in
disease - relevant studies and prioritize insights from genetics to help develop novel therapeutics; and 3) begin basic experimentation in animal
models with Crohn's
disease to provide the data necessary to begin testing new therapies in
humans.
Working
with Dr. Weiskopf, we established a
model of human dengue
disease using HLA transgenic mouse strains, and characterized
human dengue - specific CD8 + and CD4 + T - cell responses in natural infection as well as following vaccination.
We therefore suggest that the presence
of the mutated transgenes (AβPP and PS1), which are per se the basis for the genetic form
of Alzheimer's
disease in
humans, directly interferes
with gut function as shown here for the
disease model mice.
With all stages
of clinical Lyme
disease having previously been described in nonhuman primates, this animal
model was selected in order to most closely mimic
human infection and response to treatment.
The relative specificity
of this cognitive deficit points to an issue
of cognitive inflexibility in the BAC
model, which would be consistent
with deficits characteristic
of Huntington's
Disease in
humans.
«The development
of a functional
human kidney glomerulus chip opens up an entirely new experimental path to investigate kidney biology, carry out highly personalized
modeling of kidney
diseases and drug toxicities, and the stem cell - derived kidney podocytes we developed could even offer a new injectable cell therapy approach for regenerative medicine in patients
with life - threatening glomerulopathies in the future,» said Ingber.
These mouse
models are useful tools to improve our understanding
of the biological significance and functional relevance
of these polymorphisms in
human disease, particularly when validated
with controlled exposures and environmental challenges.
The mouse makes an excellent
model for
human disease because the organization
of their DNA and their gene expression is similar to
humans,
with ninety - eight percent
of human genes having a comparable gene in the mouse.
SAN FRANCISCO, CA — June 28, 2012 — Scientists at the Gladstone Institutes and an international team
of researchers have generated a
human model of Huntington's
disease — directly from the skin cells
of patients
with the
disease.