Mātai cardio science program
What shapes the human heart?
This study proposal focuses on defining the stream-line trajectory of oxygenated placental blood as it runs through the embryonic human heart tube. Can this trajectory, relative to the deoxygenated blood stream also entering the heart tube be influenced by environmental factors and does this oxygenated streamline trajectory influence the final shape of the developing heart?
Perturbations during the cardiogenesis window can lead to devastating congenital heart diseases. Complex congenital malformations with distinctive truncal outflow topologies such as Tetralogy of Fallot (ToF) and Transposition of the Great Arteries (TGA) must take shape in the cardiogenic window. There is no doubt blood flow plays a strong epigenetic role in cardiac development, however the description of blood flow patterns, both normal and deranged, is contentious and there is no unifying process yet identified.
A blood-based model of cardiogenesis has been proposed. It assumes the red thread rotates axially along its trajectory through the heart tube and that this is fundamental to the development of the double-looped human heart. The model also shows that if the red thread does not rotate, this may set up conditions for the development of transposition of the great arteries, whereby the loops run in parallel, and over-rotation modelling shows how the hallmarks that define tetralogy of Fallot may arise. Understanding how differentially electrified blood streams behave in a confined tube may give new insights into the mystery that is cardiogenesis.
It is proposed the counter-moment electromagnetic forces generated by oxygenated (red) and deoxygenated (blue) haemoglobin units flowing in a sub-millimeter diameter tube can influence the trajectory of the separately streaming fluids and thus the final morphology of the heart.
By the nature of the proposed electromotive flow model, the differential bloodline trajectories may be affected by the degree of oxygenation or by other factors such as the external magnetic field. It is assumed that, despite water (H2O) taking the position of oxygen (O2) in the heme cavity, there exists a 2 electron difference between oxygenated and deoxygenated blood, given the strongly paramagnetic nature, or high spin state of deoxygenated blood. Because the Reynolds and Womersley numbers are low (<1) in sub-millimeter lumens, blood inertia forces (pressure, gravity) do not become significant until after the cardiogenic window has closed and the now-formed heart begins to expand.
PhD Position Available
Investigating the Trajectory of Oxygenated and Deoxygenated Bloodstreams in Embryonic Human Heart Tubes
This project aims to observe the trajectory of oxygenated and deoxygenated bloodstreams as they flow through the embryonic human heart tube and investigate whether environmental factors can influence the oxygenated streamline trajectory. The study will also determine whether differential effects of oxygenated and deoxygenated blood on downstream cardiac endothelial cells and gene expression exist.
The PhD position involves conducting a bench-top study using an in vitro embryonic heart tube model to observe the trajectories of introduced-oxygenated and host-deoxygenated bloodstreams. The study will investigate whether varying the external magnetic field or the oxygenation differential between the two streams influences the flowlines. If the null hypothesis is rejected, future testing may involve manipulating regional vitelline venous blood oxygenation levels in chicken embryos to analyse flowlines and cardiac endothelial cell genetic expression.
The ideal candidate for this position should have a strong background in physics, electrodynamics, and fluids, as well as experience in experimental work and a passion for interdisciplinary research. Strong problem-solving and analytical skills, as well as proficiency in programming and data analysis, would also be valuable.
Representation of the heart and pharyngeal arches in vertebrates as blood flow trajectories (arches are classically identified as III-VI, on left): a) fish circuit with repellent slip stream arising from crossing-point (allantoic entry – white dot), b) mixed reptilian circuit, c) human circuit (ligamentum arteriosus shown as a relict of the primordial gill trajectory – purple line). From W. Peters. Basic Science Model of Blood as an Electron-Delivery Circuit Describes the Evolution of the Human Circulation. Human Genetics & Embryology (2017)
Circulation of oxygenated (red) and deoxygenated (blue) blood in vertebrates represented as a one-way, closed tubular passage positioned relative to gravity (g): a) fish circuit (inert), b) fish circuit with repellent slip stream arising from crossing-point, c) mixed reptilian circuit, d) human circuit (ligamentum arteriosum shown as a relict of the primordial gill trajectory - purple).
