Role Of Common Genetic Variation Driving Single Cell Transcriptional Heterogeneity Across The Cardiomyocyte Lineage
Funder
National Health and Medical Research Council
Funding Amount
$882,698.00
Summary
In human tissues, most mature cells develop by differentiation from pluripotent stem cells. As they undergo differentiation, their transcriptional activity changes dramatically. Many of the genetic causes for these changes are unknown, which limits research in the use of stem cells for treating and modelling disease. This proposal addresses this problem with cardiac muscle cell differentiation by utilising recent developments in biotechnology that enables individual cells to be sequenced.
Determining Shared Genetic Control Of RNA Transcription Across 45 Human Tissue Types
Funder
National Health and Medical Research Council
Funding Amount
$264,684.00
Summary
There is strong evidence that much of the genetic susceptibility to disease acts through altering way genes are turned into proteins via RNA transcripts. One important problem in using transcriptomic data to study diseases is that the genetic control of RNA transcription is known to vary between tissues. This study will use new methods and RNA data from 45 human tissues to show the degree of common genetic control for each RNA transcript between each pair of tissues.
Evolutionary Genomics Approaches For Studying Acquisition Of Drug Resistance In Tumours
Funder
National Health and Medical Research Council
Funding Amount
$313,390.00
Summary
Chemotherapy often fails because some of the cells in tumour evolve resistance to the drugs the patient is given, causing relapse. We study how a tumour’s unstable genome and high rate of mutation drives its evolution by observing tumour cells in the laboratory as they evolve resistance to drugs and the genetic differences between resistant and sensitive cells. This work will help develop therapeutic strategies to prevent tumours from evolving resistance to chemotherapy.
Using Systems Biology To Model And Predict Human Diseases
Funder
National Health and Medical Research Council
Funding Amount
$423,326.00
Summary
In the last decade, technological advances have driven the study of biology towards the statistical and computational sciences. Researchers are now able to differentiate and quantify biomolecules at levels previously unimaginable, allowing us to study their interactions and relationships to health and disease in an unbiased, systems-level manner. With expertise in bioinformatics, biostatistics and systems biology, I am uniquely placed to address these challenges.
Methods to infer dense genomic information from sparsely genotyped populations. Prediction of phenotype based on DNA polymorphisms or sequence has important applications such as prediction of disease risk in human medicine and prediction of genetic value in plant or animal breeding. This project will enhance precision and lower the cost of association studies leading to substantial increase in accuracy of such predictions. This will allow more effective genetic improvement, particularly of diff ....Methods to infer dense genomic information from sparsely genotyped populations. Prediction of phenotype based on DNA polymorphisms or sequence has important applications such as prediction of disease risk in human medicine and prediction of genetic value in plant or animal breeding. This project will enhance precision and lower the cost of association studies leading to substantial increase in accuracy of such predictions. This will allow more effective genetic improvement, particularly of difficult but important traits such as disease resistance, reduced green-house gas emissions and product quality. The same methods can be extended to improve genetic improvement in plants and better prediction of human disease risk. Read moreRead less
Discovering sex determining genes in a reptile with genetic and environmental sex determination. Reptile sex determination is particularly fascinating because it is triggered either by genes on sex chromosomes or by the nest temperature. This project will identify and characterise candidate sex determining genes in a model reptile to understand how genes control sexual differentiation and how they interact with temperature.
Was an ancient bird-like sex chromosome system ancestral to reptiles and mammals? Recent discoveries reveal amazing similarity in the sex chromosomes of distantly related animals. This project will use advanced DNA technology to explore diverse sex chromosomes in reptiles to discover whether this signifies ancient and unsuspected common ancestry, or the convergent redeployment of genes and chromosomes predisposed to determine sex.
Expanding and resolving the earliest modern human divergence through DNA. This project aims to expand and resolve the earliest modern human divergence. Although it is clear modern humans emerged from Africa, there is no consensus on the timeline of modern human evolution. Archaeological evidence suggests two contenders: east and southern Africa. Genetic data supports the latter; the team’s own data shows that the southern African KhoeSan click-speaking forager peoples have the oldest extant huma ....Expanding and resolving the earliest modern human divergence through DNA. This project aims to expand and resolve the earliest modern human divergence. Although it is clear modern humans emerged from Africa, there is no consensus on the timeline of modern human evolution. Archaeological evidence suggests two contenders: east and southern Africa. Genetic data supports the latter; the team’s own data shows that the southern African KhoeSan click-speaking forager peoples have the oldest extant human lineages. This project will generate large mitochondrial genome and whole genome sequence data for KhoeSan lineages. This is expected to narrow the time of modern human emergence.Read moreRead less
Identifying the diversity and evolution of loci associated with adaptation to aridity/heat and salinity in ancient cereal crops. This project will use ancient grains of wheat, barley and rye to find 'lost' genetic diversity at key genes associated with resistance to aridity, salt and disease. This project will make the proteins of key genes, and study their interaction with the environment over time by measuring ions in the grains to reveal the ancient environmental conditions.
The evolution of recombination cold spots during speciation. In the absence of geographic barriers, sexual reproduction between diverging populations is the greatest obstacle to the formation of new species. As diverging populations accumulate differences by the action of natural selection, genetic recombination resulting from sexual reproduction eliminates them. As a consequence, cases of speciation with gene flow such as sympatric or parapatric speciation have been considered improbable. This ....The evolution of recombination cold spots during speciation. In the absence of geographic barriers, sexual reproduction between diverging populations is the greatest obstacle to the formation of new species. As diverging populations accumulate differences by the action of natural selection, genetic recombination resulting from sexual reproduction eliminates them. As a consequence, cases of speciation with gene flow such as sympatric or parapatric speciation have been considered improbable. This project will investigate novel hypotheses for the formation of new species in the face of gene flow, and will evaluate empirically their predictions using the groundsel Senecio lautus. Results derived from this investigation will provide novel insights into the old riddle of speciation with gene flow.Read moreRead less