Author Archives: Kathleen Beben

Sometimes Science is a Circle

Over the course of the summer, we have had the privilege of listening to the work and academic/ life trajectories of some of Duke’s most distinguished faculty. These Faculty Talks have been enlightening as they keep us informed about the scope of incredible research happening at this research powerhouse of a University, and have given us a sense of directions we can take as we journey through science. The path to research is not linear, and this has really been highlighted by the different trajectory of each speaker. In this post I will highlight one talk which I found really interesting.

Dr. Jenny Tung completed her undergrad at Duke, and is now an Associate Professor in the Departments of Evolutionary Anthropology and Biology here. Her work centers on the intersection between genes and ecology, specifically investigating how behaviors and environment impact genetic variation, and how differences in genes impact behavioral outcomes. She studies the evolutionary consequences of social relationships and their causal effects on gene regulation. Her work is untraditional in that she spends her time observing primates in the wild – a model system which, albeit fairly uncommon, displays social behaviors similar to that of humans.

Primates, namely Rhesus monkeys, when organize themselves into social categories of dominance – like in humans, every clique has a leader and follows of differing status. The Tung lab has shown that social status within groups effects stress response to an environmental challenge, which then effects the behavior and cell pathogenic response. Those at a higher social status more effectively respond to challenges and those least social were hit harder with the challenge.

Basically, make friends or you will die. (at this point I began quantifying my own social patterns, making note to keep in touch with all my friends)

Dr. Tung knew she had a calling to research and knew she wanted to lead her life partly doing field work while also looking at data and running a research team. Your work will become your life, so it is important to structure your work in the way that you would like to structure your life. And, sometimes, the place where you start is the place where you will end up – with new perspectives created during the time it took to circle back. Maybe if not linear, the serendipitous nature of science is circular. What these faculty talks have taught me is that everything is connected, and everything will fall into its place.

Thank’s for reading, and stay tuned for the final blog post coming up soon.

Abstract: A Summary of my Work

A concise, working summary of my summer project:

Microglia are resident immune cells in the brain, and are necessary in establishment of normal neural circuitry, namely synapse formation and synapse refinement and elimination. Combinations of genetic predisposition and environmental factors, and maternal stress have been implicated in the maldevelopment of microglia, and predictive of neurodevelopmental disorders, like autism spectrum disorder. Previous work has shown that combined prenatal stressors induce precocious thalamocortical synapse formation and excessive synapse elimination in the anterior cingulate cortex (ACC), a brain region important for communication and social behavior. This study sought to further characterize the normal developmental pattern of synapses as impacted by microglia in the ACC. Using immunohistochemistry staining and confocal imaging we quantified both synapse number and engulfment of presynaptic particles by microglia in early developing mice to define normal formation and elimination of glutamatergic synapses in the ACC. Preliminary findings show increase in synapse number until peak time point, which then levels out around developmental day 13 in mice. Using this data we can use similar methods to compare how air pollution, a leading environmental precursor to autism, and maternal stress alters normal development of neural synaptic circuitry at peak timepoints, and its relation to autism like behavior.

There are Good Days, and There are Bad Days for Science

Hello everyone! For this week’s blog entry I’ll bring you through a day in my life working in the Bilbo/ Eroglu lab. My day begins with an 8am wake-up and a half hour of frantic pre-work preparations. Somehow during this time I manage to shower, dress, make breakfast, pack lunch and run out the door to catch the 8:30am Swift Express bus to West Campus. This bus is crucial. Missing the Swift Express means being late for the 9am start of the work day. 

Once in lab, I check in quickly with my mentor, a final year PhD student, Carina, about my daily schedule. Because most of my time is spent on software/ equipment owned through Duke’s Core Research facility (expensive and/ or large equipment which the University only owns a few of and are thus shared between all of the labs on campus) I am able to dictate my own daily schedule based upon availability of the Core machines. It is through this University program that I am able to image slices of brain tissue on a Zeiss 880 Confocal (which is super cool!), deconvolude these images (reduce background noise and make more clear) on a software called Huygens, and create 3D reconstructions of the microglia I image in software called Imaris. 

By 10am I am set up to use one of these softwares – Zen (used on the confocal microscope), Huygens, and Imaris which takes up most of my days, depending on what stage in analysis I am in. While I am grateful that the University has licenses to these programs which allow me to visualize microglia cells and synapses within the brain, it is incredible how much of my day is spend troubleshooting such expensive software. 

By noon, Imaris has probably crashed at least twice (see attached photo), and Huygens failed to process my images. While I troubleshoot or re-do lost work, I eat lunch, usually snacking throughout the day as opposed to taking a long break. I take “lunch” time to organize data which I’ve acquired, schedule more time on Duke Core Research machines, or chat with lab members. 

3:30pm: Coffee time!

You can usually find me in lab until around 6pm, after which I’m either too hungry to go on without proper dinner, or too annoyed at how long a particular program is taking to render my data. I trek home, catching the Swift Express back.

In the evening I gym, cook dinner, and watch some Netflix until I crash for the night, ready to do it all over again tomorrow!

Sometimes if I wish hard enough, it responds

Me with the scope!


Microglia May be My Favorite Cells, but Astrocytes are a Close Second

This week during our morning meetings, each person in this year’s BSURF cohort gave an 8ish minute presentation about their research project, called a Chalk Talk. It is what it sounds like – no prepared visuals other than those you can draw on the board, making what you say and how you say it even more instrumental in the coherence of the talk. Hearing about everyone’s research was super cool, and one that stuck out to me was by Sophie, who spoke about her work relating to astrocytes and the CTNND2 gene.

This summer Sophie is working as part of the Eroglu lab, which does similar work to Staci Bilbo’s lab, which I am a part of this summer. So, it was really cool to hear about a peer diving in to a similar field of research. In her talk, Sophie stressed the importance of astrocyte cells: the most abundant glial cells in the mammalian brain as being critical regulators of brain development and physiology through their interactions with synapses and neuronal communication. Microglia (which I am looking in to this summer) and astrocytes are often considered together as instrumental cells in the brain for immune function and synapse regulation. As she has mentioned in her previous blog posts, Sophie is working with the CTNND2 gene and its role in production of the delta-catenin protein. Previously thought to exist only in neurons, this protein has recently been identified in astrocytes as well! This is really interesting, and poses the question of how alterations in this gene, and subsequently this protein, affect astrocyte cell adherence and general function.

I thought Sophie’s talk was very well structured: she spoke clearly, eloquently and her visuals (of astrocytes, her knock down CTNND2 paradigm, and synapses) were clearly well thought out. Because her research is so closely related to mine, I’m especially interested in the results of her work and the relation of CTNND2 in the ACC, a region of the brain heavily implicated in autism, and the brain focus of my project. The world of neurogenetics has taken us both by storm, working our brain’s to figure out how our brains work.


“I Just Really Love Microglia”

Like neurons, the journey of a research career can be characterized by its plasticity.

This week I was privileged to sit down with Dr. Staci Bilbo (who was able to squeeze me in despite her hectic traveling schedule) and get to know her both as a PI and as an individual. Special thanks to Dr. Bilbo for sharing with me her story!

Beginning her academic path as a psychology major, Dr. Staci Bilbo’s introduction to research was not one of glia cells (her main focus, currently) but rather of neuroethology, the study of animal behavior and its underlying mechanistic control by the nervous system. For two years of her undergraduate time at Texas Tech she really enjoyed working with frogs, lizards, and various other types of reptiles to understand the neural underpinnings of navigation and communication in the hippocampus. The lab environment was fun and creative, such a positive start propelling Dr. Bilbo to continue a path of research. From here she moved to Johns Hopkins wherein she worked to understand the effects of biological rhythms, both daily and seasonal, on immune activity and efficiency. To do this she used the Siberian hamster (the animals literally collected and shipped to the U.S. by a team in Siberia!). These animals shift both the colors of their coats, and the workings of their immune response during different seasonal periods; their fever responses are shorter in the winter to the decrease metabolic strain of prolonged sickness. It was not until after this, that Dr. Bilbo really became interested in brain immunity and, after taking a neuroimmunology course at Hopkins, discovered her passion for microglia: the macrophages of the brain. This grand interest in microglia cells drove the rest of her career, even through hard times. Dr. Bilbo reflected on a great obstacle of her trajectory: when her lab at Johns Hopkins moved to Ohio State University while she was a grad student, and she was the only PhD candidate who chose to move as well. Though, she attributes the collaborative projects which resulted from this move as instrumental to her career, despite the being taxed by the move.

After a postdoc at Colorado, Boulder, she established her microglia focused lab at Duke, examining the impacts of environment on development. Talking about microglial cells, her passion for the topic was clearly evident, best summed up by her simple phrase: “I just really love microglia.” About 2 years ago, Dr. Bilbo was recruited by Harvard to begin and oversee a pre-clinical/ basic research segment of the Lurie Center for Autism as MassGeneral hospital. While this opportunity holds fond memories, the Bilbo lab is currently moving back to Duke. Personally, Duke is where Dr. Bilbo feels most at home, though a portion of the lab will remain headquartered at Harvard, noting a great chance to make the most out of available resources.

While movement throughout her life and career seems very common, it goes to show the unpredictability of one’s path, and the non-linear reality of doing what you love. Very excited about the Bilbo lab’s re-joining of Duke’s community, and the cool projects to come.

The Macro Impact of Microglia

To know how something differs when it’s broken, it must first be known how it excels when it’s fully functional.

Autism is a spectrum disorder characterized by deficits in communication and social behavior, most commonly diagnose in boys. While autism is heritable, and there have been numerous genes identified with direct correlation to autism, genes alone cannot explain development of the disorder. Hundreds of environmental factors have been implicated in autism, like chemicals, drugs, fuels, heavy metals, and dietary factors. Though, when studied in isolation, like many studies have done, either genes or environmental factors alone are only weakly predictive of autism onset.

My mentor has created a mouse model of combined prenatal environmental exposure to link the effects of environmental factors and maternal stress to alteration of brain histology causative of autism. Specifically, this summer I will be studying a region of the brain called the anterior cingulate cortex (ACC), which is important for emotion processing, learning, and memory. The focus is on cells called microglia, the brain’s resident immune cells necessary for neurologic immune response, proper central nervous system function, and are crucial for the formation of synapses. So far, the normal developmental pathway of microglial cells in the ACC has never been characterized, and it is unknown how prenatal stressors alter synapse number at different developmental time points. That’s where my data will hopefully come in. After characterizing the normal developmental pathway of microglia in developing mice brains over five developmental time points, the data will allow us to consider how toxins and prenatal stressors alter this normal developmental pathway. Likewise, it is unknown whether alteration in synapse number is due to lessened synapse formation or heightened microglial engulfment (elimination) of these synapses.

To answer these questions I’ve been working on staining brain tissue to be able to look at microglial cells through a confocal microscope and then reconstructing these 3D images through various computer programs. I like to think of it as a fancy photography project, one which will hopefully result in some really awesome conclusions and a colorful poster. I’ve been loving my time so far, and can’t wait for what’s to come.

A Whole New World (of microglia, imaging, and research)

A year ago, I had no idea what doing “research” meant. The idea, concept, and process always seemed incredibly abstract and foreign, the word eluding to images of sterile rooms filled with people wearing white lab coats seriously tinkering with mysterious liquids in shiny tall beakers. While this vision may seem to hold true upon quick glance at a research lab, stepping into the world of research and joining a research team has been a stark contrast to my previous stereotyped belief of what research is. While lab benches are filled with rows of various liquids and solutions yet unknown to me, the Bilbo/ Eroglu team which I have been working with is filled with approachable, kind, and funny people. One of my hopes for these next few summer weeks is to become integrated into the lab dynamic, gain greater independence, and be viewed as a worthwhile contributor to the project.

Speaking of the project I’ll be working on, for the next two months I’ll be spending my time characterizing the normal developmental pattern of excitatory synapse formation in the anterior cingulate cortex region of the brain, and working towards assessing if and how prenatal exposure to combined stressors alters this development. What this means is I’ll be staining brain tissue obtained from developing mice to be able to image using a confocal microscope then performing image reconstructions to allow for quantification of synapses over various time periods. Plainly said: mark up, image, enhance, then count. So, this week I have been getting familiar with the necessary techniques, machines, and softwares – getting as up to speed as I can. It’s really exciting to think about the novelty of this work, and to think that my data could describe something which has never before been known.

Dipping my feet into work which those who I’m joining in the lab have been studying for years continues to be daunting – it took me nearly the whole first week to really understand the questions I’d be attempting to answer – but I hope that over time I’ll be able to speak confidently about all things brain tissue, microglia, and imaging. I hope to obtain meaningful data, and decipher what the value of doing research will mean, to me.

I’m looking forward to whatever hits in these next few weeks. Welcome to the blog!

Me with one of Dr. G’s (non-venomous, and un-named) snakes!