Studies in humans and model organisms have shown that defects in centromere function result in chromosome abnormalities and copy-number changes that constitute a major cause of aneuploid-related syndromic disorders, intellectual disability, infertility, pregnancy loss, and cancer. Understanding the biological properties and functions of the centromere is therefore a high priority for health research.
Epigenetic Hyperglycemic Cell Memory Causes Vascular Complications In Type 1 Diabetes
Funder
National Health and Medical Research Council
Funding Amount
$332,140.00
Summary
This project seeks to identify how epigenetic change in response to hyperglycemia can cause vascular complications of diabetes, and how this contributes to “hyperglycemic memory”; a phenomena where cells may undergo gene modifications which increase risk to further complications later in a patients life. These studies are the first of their kind and will characterize the types of epigenetic change that can cause human disease.
I am a geneticist using multidisciplinary genetic and genomic approaches to study transcriptional mechanisms and molecular pathogenesis in autoimmunity and haematological malignancies.
Variation And Inheritance Of Retrotransposon Epigenotype In The Mouse
Funder
National Health and Medical Research Council
Funding Amount
$355,500.00
Summary
It is often assumed that traits in humans and other mammals are a product primarily of information encoded in the sequence of DNA, with some contribution from the environment. However, there is clear evidence that traits may vary widely between individuals with precisely the same DNA, such as identical twins, even in circumstances where environmental differences are negligible. This variation can be produced by epigenetic factors chemical changes or protein binding to DNA that alter the way gene ....It is often assumed that traits in humans and other mammals are a product primarily of information encoded in the sequence of DNA, with some contribution from the environment. However, there is clear evidence that traits may vary widely between individuals with precisely the same DNA, such as identical twins, even in circumstances where environmental differences are negligible. This variation can be produced by epigenetic factors chemical changes or protein binding to DNA that alter the way genes are used. Epigenetic factors can be passed from one generation to the next like the DNA itself, and this can make it difficult to know if a trait is encoded in the DNA itself or is epigenetic. We have found that some epigenetic traits in mice are caused by retrotransposons, which are parasitic elements that reside in and among genes, and can reproduce themselves, but do not have any known function (nearly half the human genome is made up of retrotransposons). Retrotransposons are generally kept silent by epigenetic factors, but may sometimes become active; when they do they may disturb normal patterns of gene activity and cause changes in traits and even disease. Much variation in humans may thus be due to variation in the epigenetic state (epigenotype) of retrotransposons. We propose to investigate variation and inheritance of epigenotype in mice, focussing on retrotransposons. We will use simple methods to compare epigenotype of a number of retrotransposons in genetically identical mice, and we will ask if any differences we find are heritable. We will also investigate the resetting of epigenotype the point in development when epigenetic factors are cleared and reset. We suspect that this occurs in early development. These studies may reveal a system of variation and inheritance with rules completely different from those found by Mendel, which may have a pervasive influence on traits, including sporadic diseases in humans.Read moreRead less
Investigation Of The Role Of Epimutation In Programming Of Obseity And Diabetes
Funder
National Health and Medical Research Council
Funding Amount
$333,669.00
Summary
Substantial evidence indicates that in utero environment influences the risk of developing some diseases later in life; this is known as fetal programming. We hypothesize that the in utero environment alters epigenetic marks in the fetus and changes gene expression, leading to disease later in life. We will investigate epigenetic changes in mice born to obese mothers. Better understanding of the mechanisms underlying fetal programming will result in improved administration of public health.