Tag Archives: Marija Zanic

Vanderbilt staff works throughout disciplines to copy

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A Vanderbilt College laboratory led by Marija Zanic, assistant professor of cell and developmental biology, has demonstrated for the primary time how microtubules—filaments which can be important to a lot of a cell’s capabilities—transfer round in a course of often called treadmilling.

Marija Zanic (Anne Rayner, Vanderbilt College)

“With out an interdisciplinary method and the power to simulate the experiment, the analysis would have been a futile try.” 

Microtubules are vital in capabilities starting from cell division to a cell’s means to retain its form. Understanding the method of how these filaments use vitality to inch across the cell inside, rising at one finish and shrinking on the different, might unlock insights into potential illness therapies.

An article in regards to the analysis, “Collective results of XMAP215, EB1, CLASP2, and MCAK result in sturdy microtubule treadmilling,” was revealed on-line within the journal Proceedings of the Nationwide Academy of Sciences on June 9.

Utilizing high-end microscopy, Zanic and her staff studied microtubules outdoors of cells and away from the proteins that affect their habits. From this vantage level the group noticed the important dynamics of treadmilling and experimented by including quite a lot of proteins and reagents to the microtubules to see what would change.

The lab was in a position to observe the consequences of quite a few totally different “protein recipes” with a pc simulation approach, fairly than take a look at mixtures in an infinite collection of experiments. With pc modeling, the staff discovered that combining tubulin and 4 different proteins encourages the identical form of treadmilling that happens naturally inside cells. That is the primary time that any analysis group has been in a position to replicate this habits outdoors of cells and carries probably widespread alternatives for future analysis.“With none further proteins, microtubules by themselves moved slowly and in the other way of what we see in cells,” mentioned Goker Arpag, the paper’s co-first writer and a postdoctoral analysis fellow within the Zanic lab. It was solely after researchers added protein parts that they might replicate treadmilling habits.

Goker Arpag (Vanderbilt College)
Beth Lawrence (Beth Lawrence)

By figuring out the particular proteins that modulate a cell’s perform, scientists could possibly develop therapies for illnesses and well being situations linked to microtubule habits. “If we will get these polymers to do what we would like—on this case to change the method of treadmilling—we now have the power to manage cell habits,” mentioned Zanic, additionally assistant professor of chemical and biomolecular engineering and biochemistry.

As a result of microtubules are answerable for cell division and are targets for chemotherapy, this analysis is broadly relevant to cancer-related analysis. This analysis additionally has relevance for quite a lot of neurodegenerative illnesses together with Alzheimer’s and Parkinson’s illnesses, since tubulin is a extremely plentiful protein within the human mind, important for its improvement and performance.

“This was a real collaboration between physics and biology, a really satisfying synergy,” Zanic mentioned, noting that the lab’s researchers span disciplines starting from engineering to cell biology. “With out an interdisciplinary method and the power to simulate the experiment, the analysis would have been a futile try. Computational modeling saved our lab the innumerable experiments that in any other case would have been wanted to pinpoint the particular mixture of proteins that we’ve recognized.”

Simulations predict sturdy plus-end-leading treadmilling within the presence of MAPs. (Arpag*, Lawrence* et al.)

This analysis was funded by Nationwide Institutes of Well being grant R35GM119552, Built-in Organic Programs Coaching in Oncology T32 Coaching Grant CA119925, the American Coronary heart Affiliation Predoctoral Fellowship 19PRE34380083, and Zanic’s Searle Students Program and Human Frontier Science Program Profession Improvement Awards.

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The plus and minus of microtubules | VUMC Reporter

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by Bill Snyder

The September issue of the Journal of Cell Biology featured the research of Marija Zanic and colleagues on the cover. The image is a montage of dynamic microtubule extensions (teal) grown in vitro from stabilized microtubule seeds (red).

Microtubules are protein polymers that assemble into dynamic structures, essential for cell division, shape, motility, and transport of intracellular cargos.

Proteins that regulate microtubule function and activity have been implicated in disorders ranging from Alzheimer’s disease to cancer. By learning how microtubules work, scientists hope to find new ways to treat these diseases.

The “plus” and “minus” ends of microtubules switch between growing and shrinking, a phenomenon known as “dynamic instability.” Now Marija Zanic, PhD, and colleagues have discovered that the distinct rate at which tubulin protein subunits dissociate (the tubulin “off-rate”) underlies key dynamic differences between the two ends.

The researchers also found that a minus-end directed motor protein, the human kinesin-14 HSET, promotes minus-end stability by suppressing the minus-end tubulin “off-rate,” even when challenged by the de-stabilizing kinesin-13 MCAK motor.

Their report, published in the September issue of the Journal of Cell Biology and featured on the cover, suggests that regulation of both the plus and minus microtubule ends is integrated to form the basis for the dynamic architecture of cellular microtubules.

This research was supported by the National Institutes of Health (grants GM119552, GM086610, GM008554), the Human Frontier Science Program and the Searle Scholars Program.

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