This spring found five MCB postdoctoral fellows earning valuable fellowships. Summer Thyme and Jeff Farrell from the Schier Lab and Abhishek Shrivastava from the Berg Lab all won NIH Pathway to Independence Awards. Joseph D. Zak from the Murthy Lab won the NIH NRSA fellowship, and Ding Liu from the Dulac Lab won a Jane Coffin Childs fellowship.
Thyme’s research uses zebrafish to study the genes associated with schizophrenia. Using recent techniques such as targeted genome editing, whole-brain activity imaging, brain atlas registration, and behavioral profiling, Thyme wants to analyze how these genes contribute to psychiatric disorders through disruption of molecular, cellular, developmental and behavioral processes. From her summary:
“In preliminary studies, we created mutants for over one hundred schizophrenia-associated genes. Characterization of these mutants for altered brain anatomy and activity has revealed over one third have phenotypical abnormalities. Loss of one of these genes, an uncharacterized transcription factor, resulted in a reduction of GABAergic inhibitory neurons in the forebrain and increased brain activity. This finding is particularly exciting because lower numbers of GABAergic neurons is a known phenotype of schizophrenia patients.”
Farrell’s proposal, titled “Error Correction in Early Embryos,” also makes use of zebrafish to “understand how embryos prevent and correct errors during early development, enabling them to develop normally in spite of challenges.” The first part of his research will focus on early embryonic recovery from DNA damage. From his proposal:
“Spontaneous DNA damage is unavoidable, resulting from sources like UV light and errors in copying DNA as cells divide. Previously, I found that when cells in early zebrafish embryos encounter DNA damage, they activate some additional genes that are not normally involved in this kind of response. I aim to find out what happens to cells in the early embryo that experience DNA damage and what is the role of these unusual genes that are activated in this case.”
The second part of his project will focus on abnormal cellular patterning in embryos.
“An embryo is initially composed of cells that have the potential to become any tissue in the body, and during development, individual cells are instructed to generate different tissues, so that a full organism is produced. This process is called patterning, and is usually very reproducible from animal to animal. However, I plan to study a mutant that is much less reproducible – it initially does not pattern progenitors for some tissues, but then over time corrects and usually develops into a normal fish. I will test how this correction occurs and whether the different developmental history of these cells has a lasting effect.”
Shrivastava’s proposal, titled “Dynamics of the bacterial type IX secretion system and its effect on biofilm formation by bacteria of the human microbiome,” earned him an NIH fellowship to study bacterial motion and gliding bacteria’s type IX protein secretion system (T9SS). From his proposal:
“Gliding motility, which is the output of the dynamics of T9SS, will be used to study a sensory transduction network that provides mechanical and chemical cues to trigger the formation of biofilms. Aggregates of cells that contain gliding bacteria are motile. Cells in such aggregates will be tracked in three-dimensional (3D) space and fluid flow patterns will be marked. The proposed study aims to identify how single cells decide to form communities, and how, using molecular machineries, they localize themselves along a preferred spatial niche in communities.”
Zak’s research takes him inside the workings of animal olfactory systems, specifically the transmission of odor information from neurons in the nasal cavity to the brain’s olfactory bulb. He is ultimately interested in a better understanding of how the brain processes information about an animal’s odor environment. From his proposal:
“The focus of my project is understanding how neurons in the nose encode salient features of the olfactory environment including odor identity and intensity. My research uses optical-based methods to measure the activity of populations of olfactory receptor neurons in live mice while manipulating their odor environment. As a second component of this project, I am studying the diversity of activity between neurons responsible for detecting the same odor in an effort to determine whether non-redundant information about odor stimuli is preserved by receptor neurons.”
Liu’s work, title “Neural control of social motivation,” focuses on the neural aspects of animal social grouping and isolation, specifically the psychological and physical impulses that encourage animals to re-engage in a social group after a period of isolation. From his proposal:
“In this proposed project, I will identify the brain regions and cell types that are activated during social isolation and re-grouping. Utilizing cell-type targeted calcium imaging, I will monitor the neuronal dynamics during distinct social motivation states and specific social behavioral events. To further investigate underlying circuit-level mechanisms, I will examine the synaptic connections between regions associated with isolation and grouping, and how synaptic strength changes during social isolation. Finally, cell-type and projection specific optogenetic manipulations will be conducted to regulate social motivation and alter the relevant social behaviors. This project will shed new light into the regulation of social motivation both at the cell-type and circuit-levels.”