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Welcome to the Kaplan Lab at UC Davis

Budding yeast after replication stress. The circle indicates the position of the nucleus. Nvj1 (red) shows the targeting of part of the nucleus to the vacuole and the relative position of Fob1, a nucleolar marker. (Image credit: Jonathan Do and Ken Kaplan)

 

Research Interests:

My lab focuses on cellular pathways that preserve genome integrity during mitosis. We are especially focused on anaphase and how the major events of anaphase are coordinated with DNA replication to ensure proper sister chromatid resolution. In studying these pathways, we have grown more generally interested in how normal cells transition into disease states, states that support aneuploidy in cancer or that result in progressive failures in cell functions in neurodegenerative disease. 

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ThisIBelieve about our shared biology

The educator and biologist, Bryan Dewsbury, inspired me to better understand my students by asking them to participate in the ThisIbelieve.org project. The more I thought about this project the more convinced I became that it’s important to establish a space where we (students and me) can have an open, honest dialogue about what matters. I used to text from the  “ThisIBelieve” project with the slight tweak that asked students to connect what they believe to their relationship with biology. In a class of >100 cell biologists, this became a theme in discovering the complexity of cellular functions. I am posting my personal example that I shared with the class and then I will post a stream of consciousness summary of their beliefs that I read aloud in class.

I believe that the exploration of our shared biology is implicitly revolutionary. There are many events and experiences that led me to this belief, but a stand-out experience has to do with my 9th grade science teacher. Brian Cullen was (and probably still is) an iconoclast, by which I mean that he questioned everything and asked us (how cool was it that he included 14 year olds??!!) to join him in questioning what we were told. Not surprisingly, Brian had a fraught relationship with parents and the school administration. In his 9th grade general science class, he cast the traditional scientific topics in terms of revolutionary thinkers. He told us the story of the scientists/thinkers who he called “the great ego busters” — those who rightly diminished the centrality of humans in the world. Darwin, who taught us that we weren’t a “chosen” species but that we descended from “simpler” life, that I later came to appreciate as not simple, but as equally remarkable.  Copernicus, who showed us that our planet was not at the center of the known universe. Freud, who argued that we are not even in control of our own thoughts, but rather our thoughts are influenced by our subconscious and events during our early development that we cannot even recall. There were other thinkers that fell into the same mold for Brian and that he sprinkled into our classes, like spices added to accentuate the flavor of a perfect recipe — Buckminster Fuller for example, “an American architect, systems theorist (whoa!), writer, designer, inventor, philosopher and futurist” (Wikipedia; read about his 1960s views on renewable energy). During this time of my life, I also experienced the uncertainty that comes from financial instability. For me, this confirmed my sense that not all was as it appeared to be and I learned to navigate these uncertainties by questioning what people told me was true. As I began to experience biological research in college, I brought my instinct to question everything with me. It contributed to my frustration with learning dogma and my thrill in discovering new things that allowed me to revisit what I thought I knew to be true.  Though using science in the service of others was also appealing to me (i.e., the medical school route – I applied), the possibility of revolutionizing how we think about our shared biology grew more and more attractive to me the more time I spent in inquiry. Over the years of thinking about the revolutionary aspect of inquiry, I have also been inspired in how it connects my professional life as scientist and teacher to my role in society. A main practice of my personal philosophy is to identify those areas of conflict and tension in our political discourse that can benefit from a “re-thinking” of our shared biology. Critically, the work of historians has taught me modesty even as I engage daily in small acts of revolution. It’s not only the ego-busters that matter, “…what matters is the countless small deeds of unknown people who lay the basis for the significant events that enter history.” (Noam Chomsky paraphrasing the historian Howard Zinn). I believe that our path forward for our world is through the revolution that comes from constant and protracted inquiry. 

BIS104, Cell Biology Students ThisIBelieve about our biology statements (summer 2022)

I believe that billions of years of biology allow for the full color of human possibilities and none of us are “unnatural”.

I believe in the safety and silence of books. 

I believe in the power of generosity and kindness and genetics. 

I believe in exercise for staying mentally and physically healthy. 

I believe in making the lives of animals better, especially dogs. 

I believe in the ability of animals to forgive us. 

I believe that uncovering the unknowns of biology are thrilling, exciting and humbling. 

I believe in the sacredness of nature and that we are part of the universe’s equilibrium. 

I believe our parents are just regular people doing their best. 

I believe in “why?”. 

I believe science should be inclusive. 

I believe I might be an imposter. 

I believe everyone should feel wanted. 

I believe biology equates with saving lives. 

I believe that biology is the foundation for mental health. 

I believe that what you eat matters.

I believe that biochemistry is the key (lock and key, get it!) to everything. 

I believe that knowledge constantly changes, but the world is still not flat. 

I believe we are all alike, mostly. 

I believe our shared biology is designed to be understood and to be used responsibly.

I believe human curiosity is our most endearing trait. 

I believe in the never-ending journey of learning and that our understanding of biology is under constant construction.  

I believe that the language of biology is not universal and requires teachers.

I believe in evolution and a creator. 

I believe in the primacy and the power of RNA machines and in the complexity of the small. 

I believe that not all data is good data. 

I believe science is about passing knowledge on to the next generation (and scientists are cool). 

I believe biology is both beautiful and tragic.

I believe that memorizing facts about biology ruins it.

I believe that not everyone has to believe what I believe [very meta!]. 

I believe we are all made of star stuff. 

I believe we uniquely perceive the world through our human senses

I believe that nurture not nature is what determines who you are as a person. 

I believe I can be more than what my ancestry suggests.

I believe that my love of biology is personal. 

I believe in finding purpose. 

I believe our biology embodies the struggles of our existence 

I believe biology is messy. 

I believe biology (and science) belong to everyone. 

I believe no mountain is too high to climb. 

I believe no one can tell me what my path is or is not. 

I believe you do not have to be a doctor.

I believe prevention is the best medicine.

I believe western medicine is not the only way to find health.

I believe our biology is in a feedback loop with society and culture. 

I believe biology is “me”. 

I believe you cannot control what happens to you but only how you react to it. 

I believe there is beauty and frustration in the complexity of biology. 

I believe understanding biology does not equal certainty and the one constant is change.

I believe that your “beliefs” are cellular. 

I believe in common-sense biology.

I believe that helping is a choice. 

I believe our mission as scientists is flawed. 

I believe science will either fix the world’s problems or make them worse and understanding this comes with great responsibility. 

I believe in the power of “it is what it is”. 

I believe my body is a science experiment and illness is the best teacher. 

I believe my life isn’t over. I believe that change is good.

I believe we have the power to change our own destiny. 

I believe in starting over.

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Connecting Undergraduates to Research

The COVID19 pandemic has forced all of us to reconsider how we explore the biological world and our priorities for fully understanding how our shared biology is connected to human and planetary health. As part of my re-thinking on how to engage undergraduate students in this exploration, I am starting a seminar course. The goal of this “Focus on Research” course is to bring students at any stage in their studies together to engage in a conversation that connects their interests in biology, their course material and their professional goals to the process of developing research questions. You can think of this as a prelude to identifying the type of research you might want to explore in more depth by contacting a lab on campus.

This new approach will undoubtedly evolve over time as I learn from students on how to best connect their passion for biology to the research process.  Teaching remotely in both the spring and summer I witnessed the energy and passion our students brought to the biology surrounding the pandemic (in the COVID19 Capstone Lab Course) and how our basic understanding of cellular function connects to human health (in the BIS104 Cell Biology Summer Course).  It fills me with great pride and hope to watch our students make these kind of connections and develop a passion for understanding what our shared biology means to them personally.  The goal of this course is to develop those connections in a more rigorous manner. The larger societal issues that were revealed by the pandemic connect us directly to the biology that we all care about: changes in ecosystems, human-pathogen interactions, chronic disease and health more generally as well as the inequities in access to “good health” in our society. This seminar course will offer students a chance to voice their concerns, connect them to our shared biology and to discover how we use data to focus our research on these important questions.

The first session will begin this fall (2020) – a little late – but I hope it will be empowering for all who join! Check out the course page (linked above) and I look forward to sharing updates with you on what research focuses the students identify this quarter.

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Our Shared Biology: what we share with plant pathogens

In posts under “Our Shared Biology”, I will share small stories about the cool things cells do and how it connects to larger questions about our shared biology, questions that we might be compelled to discuss as scientifically literate citizens. I know I’m not the only one who thinks about these issues or has great ideas about them, so please reach out and share. I’d love to hear from you! (kbkaplan@ucdavis.edu) 

Our shared cell biology: I study cells. When I meet someone who asks me what I do, I often struggle to find an answer that feels adequate. Saying “I study cells” tends to end conversations pretty fast.  So, instead I say that I study the cellular basis for disease; you know, like how normal cells become cancer cells. This is true enough and the mention of cancer, which touches so many, can start important conversations. Still, I can’t help feeling afterward that I’ve sold myself — and cell biology more generally — a bit short.  There’s a more honest and “preachy” answer to the question of “what do you do?” that percolates inside my head but never quite makes it way out. It might sound something like this: “I am a cell biologist. I study cells because knowing how they work inevitably leads me (and us) to the much larger story of who we are, where we came from and (maybe) where we are going. To tell this story, I try to understand how cells adapt to perturbations in order to maintain their identity, or fail to adapt in the case of disease. It is in understanding and ultimately connecting how cellular machines make cells so robust across the diversity of life on our planet that our shared biology can be slowly revealed, and we can begin to appreciate the enormous impact we humans have on this narrative. This is what I do.” 

If that sermon didn’t make the point clearly enough, I can also offer up countless examples of our beautiful cell biology. My favorite this week? Did you know that blast-fungal pathogens — the bane of rice farmers across the world — use autophagy and septins to create a high pressure cellular “gun” that can penetrate the cell wall of a leaf? Crazy biology, right? The really crazy thing is that we use these same cellular machines in ways that might be mechanistically verrrrry similar. Cool, huh?

Blast Fungal Pathogens (for plants): The images below are scanning electron micrographs of one of these blast-fungal pathogens (Magnaporthe grisea, aka Magnaporthe Oryzea), This critter can grow as single cells, but under the right conditions comes together to make a three cell blast, or conidium. From the image below, you could be forgiven for thinking that a major part of the conidium has been “deflated”, because you’d be on the right track! The “stuff” inside the two “deflated” cells have in fact been degraded by a process called, autophagy (cell self-eating), where the contents of the cell are “shipped” off to the degradative organelle (i.e., vacuole or lysosome). In the middle image, you now see that the “germ tube” has also been deflated but the final area, the appressorium (A), does the opposite; it swells or inflates. In fact, the movement of all the degraded contents from the deflated cells of the conidium act to create pressure, which is funneled through to the appressorium and finally to a “penetration peg” (see the cartoons on top and the right hand image) that channels the turgor pressure (up to 8.0 MPa; 40X that of a car tire) to the growing peg in order to breakthrough the plant leaf and allow this alien-invader fungus to invade and spread INTO the plant cell. Penetration and invasion — yikes (think Alien, the movie)! 

 

Electron micrographs of M. Oryzae, a fungal plant pathogen.

So what does this “Alien-like” biology have to do with our human-centric world view? Well, for one this blast-fungus is a major crop disease in rice and cereals, thus impacts the production of global food supply (not to mention having the potential to be a “weaponizable” biological weapon). We are also connected to this critter through the evolutionarily conserved cellular machinery that responds to environmental cues to organize the conidium into the invasion machine you see in the images. As the three cell conidium differentiates on the surface of the plant leaf, it begins to organize itself into distinct cellular regions by way of an understudied set of filaments called “septins”. Septins were first identified in the model organism budding yeast (S. Cerevisiae) where they were implicated in cell division. Since then, septins have been more broadly recognized to function in a diverse array of cell types in mammals. Septins are believed to be involved in forming physical barriers that regulate the diffusion of membrane proteins and contribute to the organization of such human-centric structures as primary cilia and dendritic spines, involved in key developmental signals and long-term potentiation in neurons, respectively (see example images below where “S” denotes septin structures). The  rules that guide septin assembly in these circumstances remain unclear. Could a plant pathogen help us make sense of what is going on in our brains or during human development? 

Examples of septin (see the “S”) filaments in fungi and mammalian cells. “nER” marks the nuclear endoplasmic reticulum.

The answer to that question is “to be determined”, but the key idea here is that it SHOULD be determined. Fungal genetics has already provided some important clues as to the signals that are important for septin organization during appressorium development. The proteins that control appessorium development are recognizable to students of human biology as parts of canonical signaling modules (i.e., trimeric G protein-coupled receptors, Ras and MAP kinase cascades, and transcription factors) that control everything from the flight-fight response to immune function in normal and cancer cells. Figuring out how these cell signal modules regulate septins in fungal plant pathogens will undoubtedly tell us something about how these same modules work in our cells. Yet, making such a case to the National Institutes of Health to study biology in model organisms, much less in a plant pathogen, is more and more an excuse to not fund a grant as it doesn’t make it over the human relevance bar. I think this overly human-centric view on biology hurts our chances to truly understand the complexity of our own biology, a biology that is part of a 4 billion year story of life on Earth that has by random chance allows us to thrive.  More generally, human-centric constructs have not generally served us or our planet well. If our society solely invests in biology that leads to the next pharmaceutical, we will be missing out on important biology that has truly transformative potential. I join a growing set of voices that advocate for bringing the modern tools of cell biology (molecular genetics, biochemistry and live cell imaging) to understanding the diverse manifestations of life on our planet as a window to truly see how our shared biology fits into the narrative of who we are and where we are going. What do you think? Email me and let me know. 

For more on how blast-fungal pathogens work and how they are connected to our conserved cell biology, check out these cool articles: 

Van Ngo, H. & Mostowy, S. Role of septins in microbial infection. Journal of Cell Science 132, jcs226266 (2019).

Hardham, A. R. in Biology of the Fungal Cell 10, 91–123 (Springer, Berlin, Heidelberg, 2001)

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Kudos to Kaplan Lab Family Success

Better late than never, right?! Help me congratulate two of our lab family on their recent accomplishments:

Alex Van Elgort was awarded an NSF Fellowship for her graduate work at Stanford University. This is quite an honor and not only recognizes Alex’s promise as a researcher, but also her dedication to educating STEM students. Congrats Alex!!

Mackenzie Noon was awarded a Provost’s Undergraduate Fellowship (PUF) to support his work on looking at rDNA array size in nucleophagy mutants. Well done Mackenzie and let’s make sure we order those reagents soon!

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Student project to develop lab course resources

Students loading SDS-PAGE in MCB140L

Learning by doing is one of the most important and yet challenging goals to translate into the undergraduate experience.  The act of “doing” allows students the chance to apply what they’ve learned in coursework to real world scenarios, to solve problems using critical thinking skills, and to reflect on how we understand the complex biology relevant to all of us. The goal of our upper division lab courses in MCB is to provide students access to learning by doing, albeit in a compressed 10-week format. I am seeking students interested in helping design new modules for the advanced cell biology lab course (MCB140L). Students will gain experience designing advanced curriculum and translating complex biological concepts and experimental approaches into practical modules. You can learn more about student projects here. Contact me (kbkaplan@ucdavis.edu) if you’re interested in participating (independent study units available).

 

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Undergrads shine in research conference 2019

Big congrats to all the undergraduate thesis students for 2019! 

Jonathan Do, an Environmental Toxicology Major and(a McNair’s Scholar,  joined the lab this year to explore how genome checkpoint pathways connect to our replication stress induced nucleophagy. Jonathan’s talents being a chemistry tutor are on full show here as he explains his thesis project to the rapt audience.

Mark Williams, a double Cell Biology and Physics major battled through computer issues to present his findings on how micronuclei, a major source of genome instability in tumor cells, might be suppressed by autophagy.

Mackenzie Noon, a Genetics major, presented his work on assessing how replication stress induced nucleophagy impacts the size of the rDNA array. Mackenzie has managed to develop a qPCR assay for measuring this chromosome array and is ready test his hypothesis.

Ariana Cisneros, a Cell Biology major, presented her work tracking autophagy membranes in wild type and septin mutant cells. Ariana has spent a lot of time staring at “spots” in time-lapse images, so it’s no surprise that she’s in need of a cold beer after her talk (and I forgot to get a photo of her actual talk!!).

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MCB140L – 2019 – Research on septins – the dark sheep of the cytoskeletal family

In the advanced cell biology lab class for Cell Biology Majors in the College of Biological Sciences at UC Davis, students learn classic and advanced techniques used by cell biologists to understand how cellular machinery contributes to cell functions. This year students analyzed the behavior of septins under various nutrient conditions. Septins are a conserved cytoskeletal filament that interact closely with cell membranes, and they have been implicated in cell division, neuronal plasticity, cell signaling and targeting of intracellular pathogens to the lysosome for destruction. Despite their very interesting biology, septins are far less studied than their “famous” siblings in the cytoskeletal family – actin and microtubules.

After conducting yeast two hybrid studies on septin subunits and membrane proteins, the 140Lers below are taking a well deserved donut-break. Analyzing data uses lots of glucose!!

MCB140Lers on donut break!

 

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Tanahashi Ryoya Visits from Nara Institute of Science and Technology, Japan

In January, we hosted Ryoya, a Ph.D student from the Nara Institute of Technology in Japan join us for a month long visit. Ryoya is from the Laboratory of Applied Stress and Microbiology at Nara, and is supervised by Dr. Takagi.

Ryoya teaching us about how to drink “brown wine”!

 

 

 

 

 

 

 

 

 

Ryoya helped us apply deconvolution algorithm to our spinning disc confocal data on septins. He learned how to use our experimentally determined point spread function data to reduce background, increase intensity and overall increase resolution of septin structures as observed below. Thanks for your hard work Ryoya and come back and visit any time.