Interested in cell division in tissues in vivo? Curious about how the mammalian brain grows so fast and why it is so vulnerable to mutations affecting cell division? The Dwyer Lab in the Department of Cell Biology at the University of Virginia seeks a Postdoctoral Research Associate to work on exciting new projects about the genes and mechanisms underlying normal and abnormal brain development. Funded projects focus on 1) how precise regulation of cytokinetic abscission in neural stem cells affects cell fate, cilia, and signaling pathways. 2) new mouse mutants with novel brain development phenotypes. To apply please email Dr. Dwyer or message her in LinkedIn or apply at UVA's Workday web page to posting "R0032622".

Neurodevelopmental disorders (NDDs) impose a global burden, affecting an increasing number of individuals. While some causative genes have been identified, understanding the human-specific mechanisms involved in these disorders remains limited. Traditional gene-driven approaches for modeling brain diseases have failed to capture the diverse and convergent mechanisms at play. Centrosomes and cilia act as intermediaries between environmental and intrinsic signals, regulating cellular behavior. Mutations or dosage variations disrupting their function have been linked to brain formation deficits, highlighting their importance, yet their precise contributions remain largely unknown. Hence, we aim to investigate whether the centrosome/cilia axis is crucial for brain development and serves as a hub for human-specific mechanisms disrupted in NDDs. Towards this direction, we first demonstrated species-specific and cell-type-specific differences in the cilia-genes expression during mouse and human corticogenesis. Then, to dissect their role, we provoked their ectopic overexpression or silencing in the developing mouse cortex or in human brain organoids. Our findings suggest that cilia genes manipulation alters both the numbers and the position of NPCs and neurons in the developing cortex. Interestingly, primary cilium morphology is disrupted, as we find changes in their length, orientation and number that lead to disruption of the apical belt and altered delamination profiles during development. Our results give insight into the role of primary cilia in human cortical development and address fundamental questions regarding the diversity and convergence of gene function in development and disease manifestation. It has the potential to uncover novel pharmacological targets, facilitate personalized medicine, and improve the lives of individuals affected by NDDs through targeted cilia-based therapies.

There is a recent surge of interest in the behavior of active particles that can at the same time align their direction of movement and synchronize their oscillations, known as swarmalators. While analytical and numerical models of such systems are now abundant, no real-life examples have been shown to date. I will present an experimental investigation of the collective motion of the nematode Turbatrix aceti, which self-propel by body undulation. I will show that under favorable conditions these nematodes can synchronize their body oscillations, forming striking traveling metachronal waves which, similar to the case of beating cilia, produce strong fluid flows. I will demonstrate that the location and strength of this collective state can be controlled through the shape of the confining structure; in our case the contact angle of a droplet. This opens a way for producing controlled work such as on-demand flows or displacement of objects. I will illustrate this by a practical example: showing that the force generated by the collectively moving nematodes is sufficient to change the mode of evaporation of fluid droplets, by counteracting the surface-tension force, which allow us to estimate its strength.

Filaments (slender, microscopic elastic bodies) are prevalent in biological and industrial settings. In the biological case, the filaments are often active, in that they are driven internally by motor proteins, with the prime examples being cilia and flagella. For cilia in particular, which can appear in dense arrays, their resulting motions are coupled through the surrounding fluid, as well as through surfaces to which they are attached. In this talk, I present numerical simulations exploring the coordinated motion of active filaments and how it depends on the driving force, density of filaments, as well as the attached surface. In particular, we find that when the surface is spherical, its topology introduces local defects in coordinated motion which can then feedback and alter the global state. This is particularly true when the surface is not held fixed and is free to move in the surrounding fluid. These simulations take advantage of a computational framework we developed for fully 3D filament motion that combines unit quaternions, implicit geometric time integration, quasi-Newton methods, and fast, matrix-free methods for hydrodynamic interactions and it will also be presented.

We study the larval stages of the marine annelid Platynereis dumerilii, a powerful experimental system for neural circuits. With serial electron microscopy, we have reconstructed the entire nervous and effector systems of a Platynereis larva. We use neurogenetics, activity imaging, and behavioural experiments to understand circuit activity and how the nervous system controls behaviour and physiology. Platynereis is one of very few systems where these different approaches can be combined to study an entire nervous system. I will talk about circuits for the whole-body coordination of locomotor cilia and a hydrodynamic startle response for predator avoidance.

It is often assumed that biological swimmers conform faithfully to certain stereotypes assigned to them by physicists and mathematicians, when the reality is in fact much more complicated. In this talk we will use a combination of theory, experiments, and robotics, to understand the physical and evolutionary basis of motility control in a number of distinguished organisms. These organisms differ markedly in terms of their size, shape, and arrangement of locomotor appendages, but are united in their use of cilia - the ultimate shape-shifting organelle - to achieve self-propulsion and navigation.

Paramecium is a unicellular organism that swims in fresh water using cilia. When it is stimulated (mechanically, chemically, optically, thermally, etc), it often swims backward then turns and swims forward again: this is called the avoiding reaction. This reaction is triggered by a calcium-based action potential. For this reason, it enjoyed a period of glory in the 1970s as a model organism for neuroscience. I will describe the behavior and electrophysiology of this “swimming neuron”, then I will present our ongoing attempts at developing an integrative quantitative model of Paramecium.