R01HD102534

Single-Cell Epigenomic Phenotyping of IMPC-Generated Mouse Lines Lacking Chromatin Regulators - Project Summary/Abstract

The epigenetic machinery is essential for mammalian development, and components of this machinery are mutated in a variety of human diseases. Hundreds of regulatory proteins participate in the reading, writing, and erasing of epigenetic information over the lifespan of an organism. However, the in vivo activity of many of these epigenetic regulators remains inadequately characterized.

Here, we leverage IMPC-generated mouse lines lacking epigenetic regulators, together with recent advances in single-cell epigenomic and transcriptomic technologies, to interrogate components of the epigenetic machinery in vivo at the molecular level, and with the cell-type resolution necessary to understand their complex roles in development and disease.

The data produced here will reveal gene regulatory defects caused by loss of epigenetic regulators in a diverse panel of tissues and cell types relevant to human congenital malformations. This tissue- and cell-type-resolved view of the effects of mutations in the epigenetic machinery is a critical step in larger efforts to reveal mechanisms of epigenetically-influenced disease risk, interpret non-coding sequence variation, and ultimately to tailor diagnostics and therapeutics to the epigenomic and transcriptomic states of a patient's disease-contributing cells.

Emory University

TO CONDUCT AND SUPPORT LABORATORY RESEARCH, CLINICAL TRIALS, AND STUDIES WITH PEOPLE THAT EXPLORE HEALTH PROCESSES. NICHD RESEARCHERS EXAMINE GROWTH AND DEVELOPMENT, BIOLOGIC AND REPRODUCTIVE FUNCTIONS, BEHAVIOR PATTERNS, AND POPULATION DYNAMICS TO PROTECT AND MAINTAIN THE HEALTH OF ALL PEOPLE. TO EXAMINE THE IMPACT OF DISABILITIES, DISEASES, AND DEFECTS ON THE LIVES OF INDIVIDUALS. WITH THIS INFORMATION, THE NICHD HOPES TO RESTORE, INCREASE, AND MAXIMIZE THE CAPABILITIES OF PEOPLE AFFECTED BY DISEASE AND INJURY. TO SPONSOR TRAINING PROGRAMS FOR SCIENTISTS, DOCTORS, AND RESEARCHERS TO ENSURE THAT NICHD RESEARCH CAN CONTINUE. BY TRAINING THESE PROFESSIONALS IN THE LATEST RESEARCH METHODS AND TECHNOLOGIES, THE NICHD WILL BE ABLE TO CONDUCT ITS RESEARCH AND MAKE HEALTH RESEARCH PROGRESS UNTIL ALL CHILDREN, ADULTS, FAMILIES, AND POPULATIONS ENJOY GOOD HEALTH. THE MISSION OF THE NICHD IS TO ENSURE THAT EVERY PERSON IS BORN HEALTHY AND WANTED, THAT WOMEN SUFFER NO HARMFUL EFFECTS FROM REPRODUCTIVE PROCESSES, AND THAT ALL CHILDREN HAVE THE CHANCE TO ACHIEVE THEIR FULL POTENTIAL FOR HEALTHY AND PRODUCTIVE LIVES, FREE FROM DISEASE OR DISABILITY, AND TO ENSURE THE HEALTH, PRODUCTIVITY, INDEPENDENCE, AND WELL-BEING OF ALL PEOPLE THROUGH OPTIMAL REHABILITATION.

93.865 - Child Health and Human Development Extramural Research

National Institute of Child Health and Human Development (NICHD) [HHS - NIH]

Atlanta, Georgia 303221007 United States

Single Zip Code

In-Depth Phenotyping and Research Using IMPC-Generated Knockout Mouse Strains Exhibiting Embryonic or Perinatal Lethality or Subviability (R01 Clinical Trial Not Allowed) (PAR-20-137)

Amendment Since initial award the total obligations have increased 377% from $719,244 to $3,429,432.