{"id":8719,"date":"2018-07-23T09:19:37","date_gmt":"2018-07-23T13:19:37","guid":{"rendered":"https:\/\/biology.mit.edu\/?p=8719"},"modified":"2020-10-29T23:15:06","modified_gmt":"2020-10-30T03:15:06","slug":"a-tale-of-two-projects","status":"publish","type":"post","link":"https:\/\/biology.mit.edu\/a-tale-of-two-projects\/","title":{"rendered":"A tale of two projects"},"content":{"rendered":"

To sixth year graduate student Julie Monda, dividing cells are among the most beautiful things she\u2019s ever seen. Watching the tiny, delicate spheres split into identical versions of themselves also provides her with a visual readout for her experiments \u2014 will the process continue if she removes a certain piece of a certain protein? Will the genetic material still distribute equally between the two cells? Which molecules are crucial for cell division, and how are they regulated?<\/p>\n

Our cells are constantly dividing in order to grow and repair themselves, although some (like skin cells) do so more often than others, say, in the brain. This process, known as mitosis, is the primary focus of\u00a0Iain Cheeseman<\/a>\u2019s lab, situated in the\u00a0Whitehead Institute for Biomedical Research<\/a>. Most of the research in the Cheeseman lab involves the kinetochore, a group of proteins located on the chromosome where the arms join. During mitosis, long, fibrous structures, known as microtubules, attach to the kinetochore to pull apart the duplicated chromosomes as the parent cell splits in half, ensuring each daughter cell receives an exact copy of the parent\u2019s genetic blueprint.<\/p>\n

Before she arrived at MIT Biology in the fall of 2012, Monda worked as a research technician at St. Jude Children\u2019s Research Hospital in Memphis, Tennessee in the lab of Brenda Schulman PhD \u201996 . As she recalls, she always \u201cpreferred performing hands-on research techniques at the lab bench over being in a classroom.\u201d So she surprised even herself when she chose MIT\u2019s graduate program in biology precisely because it requires all first-year students to take a full course load their fall semester before beginning lab rotations.<\/p>\n

\u201cThat structure seemed useful given that I studied biochemistry as an undergraduate at the University of Tulsa, and the degree requirements were weighted more towards chemistry than biology,\u201d she says. \u201cPlus, when you\u2019re only taking classes, you spend more time interacting with your classmates. It creates a close-knit community that extends throughout your entire graduate career and beyond.\u201d<\/p>\n

Monda ultimately selected the\u00a0Cheeseman lab<\/a>\u00a0because it married her interests in biochemistry and cell biology.<\/p>\n

\u201cThe research in this lab focuses on various elements of kinetochore function and cell division, but everyone is generally working on their own distinct questions,\u201d she explains. \u201cI knew I would have an area that was mine to explore. It\u2019s both exciting and challenging because no one else is thinking about your projects to the extent that you are.\u201d<\/p>\n

Monda\u2019s story is a tale of two projects: one focused on the interface between the kinetochore and the array of microtubules known as the mitotic \u201cspindle,\u201d and another project that ended up taking both her and the lab in a slightly new direction.<\/p>\n

The first, concerning kinetochore-microtubule interactions, represented a collaboration with former lab technician Ian Whitney. For this endeavor, Monda investigated a protein complex called Ska1, found at the outer kinetochore.<\/p>\n

The Ska1 complex is located where the kinetochore and microtubule meet. Ska1\u2019s role, Monda explains, is to allow the kinetochores to remain attached to the spindle during chromosome segregation, even as the microtubules that compose the spindle begin to disassemble (as they must do).<\/p>\n

\u201cWe wanted to know how the kinetochore hangs onto this polymer that is essentially falling apart,\u201d Monda explains. \u201cLong story short, we ended up defining specific surfaces within the Ska1 complex that are important for holding on to the microtubule as it shrinks, and \u2014 as we were surprised to note \u2014 also as it grows\u201d<\/p>\n

Although Ska1 only requires a single point of contact to bind a microtubule, Monda and Whitney\u00a0pinpointed multiple surfaces<\/a>\u00a0on Ska1 that are required to allow it to remain associated with the microtubules as they disassemble and reassemble themselves.<\/p>\n

While her Ska1 project was very much in line with the types of questions that the Cheeseman lab traditionally pursues, Monda also worked on another endeavor that \u201cbegan as a side project and slowly evolved into a more full-time effort.\u201d This project involves a motor protein called dynein, which helps to align the chromosomes and position the spindle during mitosis.<\/p>\n

Dynein piqued Monda\u2019s interest because of its role in mitosis, as well as its importance throughout the entire cell cycle. Motor proteins are molecules powered by the release of chemical energy that move along surfaces, sometimes transporting cargo, sometimes performing other essential tasks. Dynein is a motor protein that walks in one direction along microtubules, even when the microtubules latch onto the kinetochore to yank apart the chromosomes during mitosis.<\/p>\n

But dynein doesn\u2019t act alone. There are a number of additional proteins that also play a key role in coordinating its activity and localization. Monda is studying two of these accessory regulatory proteins, Nde1 and NdeL1, which bind to dynein and help promote some of its functions. She wanted to understand how Nde1 and NdeL1 interact with dynein to activate it. Although Nde1 and NdeL1 are nearly identical in function, Monda discovered that Nde1 (but not NdeL1) binds to another complex: the 26S proteasome.<\/p>\n

The proteasome degrades proteins within the cell, influencing virtually all aspects of cellular function, including DNA synthesis and repair, transcription, translation, and cell signaling. Given its ubiquity, it has remained a point of interest among the scientific community for years. And yet, before Monda\u2019s research, the interaction between Nde1 and the proteasome had apparently gone unnoticed. Researchers have long studied Nde1 in relation to dynein, but it\u2019s possible that the interaction between Nde1 and the proteasome represents a new function for Nde1 unrelated to dynein regulation. In fact, Monda\u2019s finding may have implications for understanding the development of the human brain.<\/p>\n

\u201cIt\u2019s clear that patients with mutations in Nde1 have much more severe neurodevelopmental defects than scientists would have predicted,\u201d Monda says, \u201cso it\u2019s possible that this new interaction between Nde1 and the proteasome could help to explain why Nde1 is so important in the brain.\u201d<\/p>\n

Her most recent results have been published in\u00a0Molecular Biology of the Cell<\/a><\/em>.<\/p>\n

\u201cI\u2019ve found some exciting results over the past few years,\u201d Monda says, \u201cand even though a lot of my research has gone in a direction that\u2019s not strictly mitosis-related, Iain has been great about allowing me to follow the science wherever it leads. We want to know what these proteins are actually doing, both in terms of this new interaction and also more broadly within the cell.\u201d<\/p>\n

Monda intends to submit and defend her thesis this summer, and assume a postdoctoral position at the University California, San Diego in the fall. Although she\u2019s been watching cells divide for years now, the process still retains its grandeur.<\/p>\n

\u201cOften times biologists investigate questions at scales where we can\u2019t really see what we\u2019re studying as we study it,\u201d she says. \u201cBut having this visual readout makes it more tangible; I feel like I can better appreciate what exactly it is that I\u2019m trying to understand, as well as the beauty and complexity of the processes that sustain life.\u201d<\/p>\n","protected":false},"excerpt":{"rendered":"

To sixth year graduate student Julie Monda, dividing cells are among the most beautiful things she\u2019s ever seen. Watching the tiny, delicate spheres split into identical versions of themselves also provides her with a visual readout for her experiments \u2014 will the process continue if she removes a certain piece of a certain protein? Will […]<\/p>\n","protected":false},"author":16,"featured_media":8718,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[1],"tags":[],"class_list":["post-8719","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-uncategorized","placement-placement-homepage","research-area-biochemistry-biophysics-and-structural-biology","research-area-cell-biology"],"acf":[],"yoast_head":"\nA tale of two projects - MIT Department of Biology<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/biology.mit.edu\/a-tale-of-two-projects\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"A tale of two projects\" \/>\n<meta property=\"og:description\" content=\"To sixth year graduate student Julie Monda, dividing cells are among the most beautiful things she\u2019s ever seen. 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