Dr. Eva-Maria Schoetz Collins is applying physical principles and techniques to investigate the fundamental biological processes of development and regeneration, with a focus on the nervous system. Dr. Collins’ research is seeking answers to three important questions: 1. What is the role of mechanical interactions of cells and their environment for tissue and organ formation during early embryonic development, 2. How do environmental neurotoxins damage brain development and function, and what can we do to prevent or reverse it, and 3. What is the differentiation process of stem cells to neurons and how can new neurons integrate into existing circuits? Understanding how an initially unstructured suspension of cells is able to autonomously organize itself into separate tissues, organ systems, and ultimately organize a fairly complex organism has potential implications for tissue and organ engineering in the lab for use in humans. Deciphering the mechanism by which exposure to environmental toxins causes neurodevelopmental defects will help design better exposure guidelines for humans and inspire new preventive therapies. For neurons that cannot be salvaged and have been damaged or destroyed, understanding the process of neural regeneration via stem cells in planarians is crucial for understanding and controlling the process in humans. The hope is to one day to be able to use stem cells for regenerative therapies for currently incurable neuronal diseases such as Parkinson’s, Alzheimer’s, and motor-neuron diseases.

Dr. Eva-Maria Schoetz Collins, Assistant Professor of Physics and Cell and Developmental Biology at the University of California, San Diego is pursuing a quantitative approach to study fundamental biological problems pertaining to embryonic development and regeneration. Her research interests are threefold: First, she seeks to understand which factors govern early tissue and organ formation during embryonic development. For this study, her group uses freshwater hydra, which have the astounding capability of whole organism regeneration after complete dissociation into individual cells, allowing her team to study how an entire animal with a distinct body plan evolves de novo from a soup of cells. Second, in another regenerative organism, freshwater planarians, Dr. Collins is looking to decipher by which mechanisms environmental toxins impair development, specifically of the nervous system. Third, she is using the same organism to study neuronal repair after specific types of neurons have been chemically or optically ablated. Though these processes are being studied in relatively simple organisms, key genes and regulatory pathways are conserved between these animals and humans, and therefore the results garnered from these experiments can lead to conclusions applicable to human development.

Dr. Collins' current research is focused on three major questions:

1. What is the role of mechanical interactions for cell migration, differentiation, and tissue formation?

   • Dr. Collins is trying to understand how pattern formation—how things grow from a single cell to a complex organism while forming different structures along the way—is achieved during development, and what the roles of physical interactions between cells and with the environment are for these processes. Experimental studies are conducted in one of the best regenerating organisms: the freshwater polyp Hydra, which autonomously self-organizes and regenerates after being completely dissociated into a suspension of single cells. In other words, one can stick hydras in a blender, make “Hydra soup” and from this blend a new animal will emerge within about a week! Because of their remarkable ability to regenerate, and their structural simplicity, Hydra regeneration is fully accessible for quantitative measurements and controlled chemical and mechanical perturbations while providing a relevant in vivo environment to make the measurements meaningful. Dr. Collins is combining quantitative measurements of mechanical properties and of cell behaviors with molecular biology experiments to determine which proteins and pathways are responsible for this remarkable self-organization of tissues during regeneration. Because fundamental mechanisms such as mechanical interactions operate in all animals, understanding a simple organism such as Hydra will help us understand this process in more complex organisms, including humans.

2. How can we effectively evaluate, prevent, and repair neuronal damage caused by environmental toxins?, and for structures not salvageable, how do stem cells coordinate to generate different types of neurons and reconnect to restore neuronal functions?

   • Dr. Collins’ lab has developed a custom screening assay that allows her team to study the influence of environmental neurotoxins, chemicals known to disrupt normal brain function, on brain development using freshwater planarians as a model system. Planarians are renowned for their regenerative capabilities which are based on adult pluripotent stem cells; if you cut a worm into 10 pieces, they will all regenerate into new little worms in about a week. This amazing feature allows Dr. Collins to generate animals that are all genetically identical for her toxin studies and thus distinguish between genetic and environmental factors which may influence their vulnerability to toxins. The planarians’ regeneration also allows her to induce brain development “at will” by amputation. To elucidate specific developmental neurotoxic effects, Dr. Collins’ group studies the effect of toxin exposure on adult and regenerating worms in parallel with the same assays, thus enabling a direct comparison of neurotoxicity in adult and developing brains. The planarian brain is much simpler than the human brain with only a few thousand neurons, yet it has sufficient complexity and similarity, sharing the same neuronal subpopulations and neurotransmitters, to be relevant for human studies. Thus, by studying the effect of toxins on planarian brain development, we can gain insight into key mechanisms for human brain development.

   • Unfortunately, in real life one is often unaware of the toxins that they may be exposed to and thus following exposure guidelines is not always possible. Therefore, The Collins Lab is also investigating how neuronal damage could be repaired after it has occurred. Her team is developing assays to use chemical and optical means to destroy a neuronal subpopulation of interest and then study the regeneration dynamics of this population. Many of the tools from the neurotoxicity screen are useful for this research project, in particular behavioral readouts to assay neuronal function. Dr. Collins has three important goals in this project: (1) screen a large number of environmental toxins to determine their effects on brain development and compare her results with data from other organisms, which will in turn help develop better exposure guideline for humans. (2) For a group of selected neurotoxins, use planarians as a model to better understand the molecular mechanism underlying their neurotoxicity and use this information to help develop better antidotes if exposure cannot be prevented. (3) Finally, again taking advantage of the planarian’s ability to regenerate, Dr. Collins is seeking to understand how the worms repair neuronal damage after toxin removal using their stem cell population. Understanding these mechanisms in the worm may provide inspiration and insight for the development of stem-cell based therapies in the future.