By Irene Hsiao
It has been a stellar year of science for UChicago Chemistry—check out these highlights from the labs and a few words from the authors.
Mechanical and kinetic factors drive sorting of F-actin cross-linkers on bundles
Published August 2019 in PNAS
From Aaron Dinner: This study presents a theory for how molecules that bind protein filaments can self-organize and verifies the theory with both simulations and new experiments. The study is important for understanding how cells can simultaneously form different protein filament structures in different regions to enable compartmentalized functions.
Fun Fact: When final author Glen Hocky took General Chemistry his first year as an undergraduate at the University of Chicago, his professor was Aaron Dinner. Little did they expect that they would be collaborating and publishing a paper together thirteen years later. Glen is now an assistant professor of chemistry at NYU!
High Throughput Discovery of Functional Protein Modifications by Hotspot Thermal Profiling
Published August 2019 in Nature Methods
From Raymond Moellering: This paper presents a new method to identify and interrogate the biophysical properties of tens of thousands of modified proteins simultaneously in live cells. This method, called “Hotspot Thermal Profiling,” enables efficient selection of functionally important post-translational modifications for further study, as well as insight into the network of proteins and biomolecules that are interacting with that particular modification site in cells.
Fun Fact: The main idea behind the hotspot thermal profiling method and its application to study post translational modification networks in cells first came to Ray around mile 8 of a half marathon!
More about the paper and first author Joey Huang
More about Raymond Moellering in the Winter 2018 Chemists Club newsletter
An atlas of nano-enabled neural interfaces
Published July 2019 in Nature Nanotechnology
From Bozhi Tian: In this paper, we reviewed the current progress in nanotechnology-enabled neuroscience studies and provide perspectives on future research development in this area.
Fun Fact: Bozhi made all the figures himself, which took more than 170 hours of work in Adobe Illustrator! “I found it quite relaxing!" he says. "The experience reminded me of drawing during my childhood. That was also a moment that I realized how art and science can be integrated in a powerful way!”
Programmable RNA-Guided RNA Effector Proteins Built from Human Parts
Published in June 2019 in Cell
From Bryan Dickinson: We created a new human parts-based technology to control gene expression at the RNA level, opening up exciting opportunities for therapeutic development.
Fun Fact: This project initially started as a side project for lead author Simone Rauch, as they thought the likelihood of it working was very, very low. Says Bryan, “It was a crazy idea that we just decided to try. We were quite surprised when the first experiments showed some promise!” Read more about Simone here.
Published April 2019 in Nature Communications
From Wenbin Lin: A nanomedicine composed of an antimalarial drug and an anticancer drug selectively produces cytotoxic reactive oxygen species to boost the body’s own immune response to eradicate colorectal cancers in mice
Fun Fact: The World Health Organization estimates that the quintessential antimalarial drug artemisinin is estimated to have saved 6.8 million lives between 2001 and 2015. Although anecdotes suggest that artemisinin might have an anticancer effect, no concrete evidence exists to support the use of artemisinin as an anticancer drug. However, because our group had successfully killed cancer cells with reactive oxygen species (ROS), we hypothesized that the endoperoxide ring of artemisinin could be selectively cleaved within cancer cells to generate ROS for anticancer effects. To realize this goal, graduate students Xiaopin Duan, Christina Chan, and Wenbo Han teamed up to design cleavable prodrugs of artemisinin and oxaliplatin, an important component of the well-established FOLOFOX chemotherapy regimen for the treatment of colorectal cancer, and formulated them into nanoscale coordination polymer (NCP) particles. To our delight, these NCPs selectively deliver artemisinin and oxaliplatin to tumors to kill cancer cells, and more importantly, this nanoparticle treatment causes immunogenic cell death to prime the tumor microenvironment for synergistic combination with checkpoint blockade immunotherapy to eradicate colorectal tumors in mice. Coordination Pharmaceuticals, a startup company founded by Wenbin, is already conducting clinical trials on two NCP formulations for the treatment of advanced tumors.
Dual-band infrared imaging using stacked colloidal quantum dot photodiodes
Published February 2019 in Nature Photonics
From Philippe Guyot-Sionnest: This paper describes a detector made with two sizes of HgTe nanocrystals. Through the quantum size effect, the small ones absorb short-infrared band that transmits through glass and is reflected or scattered from external light sources. The larger ones absorb mid-infrared band, which is emitted by warm bodies. A clever design by graduate student Matt Ackerman and Dr. Xin Tang switches between the two bands depending on the sign of the voltage applied, permitting imaging in either regimes.
In the words of one of the reviewers:
“The current demonstration of a dual-band detector with colloidal materials is super exciting”!
“All of this knowledge is assembled here in an experimental tour de force”!
“An important development that points to simple and inexpensive strategies to make new IR detectors and imagers”!
Fun Fact: Hair pigments do not absorb short infrared, so hair appears grey/white/distinguished for all.
Anti-tumour immunity controlled through mRNA m6A methylation and YTHDF1 in dendritic cells
Published February 2019 in Nature
From Chuan He: This study revealed that the mRNA m6A methylation and its reader protein YTHDF1 play important roles in spontaneous tumor immunity and identified YTHDF1 as a new target for effective anti-tumor immunotherapy.
Fun Fact: “It was a purely accidental discovery,” says Chuan. “My new postdocs were interested in DNA hydroxymethylation when they joined the group. I told them that they should work on RNA methlyation instead, and that, because YTHDF1 and YTHDF2 play important roles in determining the fate of the methylated mRNA in mammals, I suspected if they performed tumor xenograft experiments in Ythdf1 and Ythdf2 knockout mice they might see faster tumor growth compared with the wild-type host mice. Well, in Ythdf1 knockout mice they saw just the opposite! Always listen to your adviser but do not trust what they said. It took a few years to figure out why, and we may have made one of the most significant discoveries (time will tell) in the field.”
Published February 2019 in JACS
From John Anderson: Protons and electrons can move together to mediate difficult transformations such as C-H activation. In this paper, we show, however, that they can't move too closely together and that these reactions are actually faster when there is a little bit of temporal separation between the protons and the electrons.
Fun Fact: When graduate student McKenna Goetz and Anderson were doing this work, they didn’t initially believe in their own results, as they contradicted nearly all of the literature of the past two decades. Says Anderson, “It was only after some long and thorough experiments that we convinced ourselves that the trends we saw were real. Since we’ve published this, a number of other groups around the country and world have observed similar phenomena, which makes us feel a bit better about our conclusions!”
Deacylative transformations of ketones via aromatization-promoted C–C bond activation
Published January 2019 in Nature
From Guangbin Dong: The paper describes a new organic synthetic method developed in our lab, which provides unusual but useful transformations of ketones, a fundamental organic functional group.
Fun Fact: The method was discovered by graduate student, Yan Xu, who graduated a year ago. Originally, Yan was hoping to develop a C-H bond activation method based on his previous work (J. Am. Chem. Soc. 2017, 139, 5716-5719); instead, he got an unexpected result. After careful analysis and investigation, Yan succeeded in developing this C-C bond activation method!
Published December 2018 in Light: Science and Applications
From Norbert Scherer: We discovered that optical matter systems - nanoparticle constituent elements bound together by light - can exhibit driven dynamics that appear to violate Newton's third law, the actio et reactio principle
Fun Fact: Norbert says, "The measurements revealed a series of bizarre observations; optically bound dimers would sometimes move deterministically in one direction or the other around the ring of light, while other optically bound dimers would simply move diffusivity. We realized that size matters: viewing them as a single asymmetrical electrodynamic object, heterodimers scatter light asymmetrically while homodimers do not, so dimer motion results from conservation of momentum. Newton can rest easy!"
A DNA-based fluorescent reporter maps HOCl production in the maturing phagosome
Published December 2018 in Nature Chemical Biology
From Yamuna Krishnan: Our immune cells trap harmful pathogens in a subcellular compartment called the phagosome, which rapidly turns into a chemical cauldron filled with toxic reactive species where the pathogen is chemically cooked. Our lab developed the first method to watch pathogens meet their grisly end in real-time by mapping the reactive species HOCl in the phagosome of immune cells.
Fun Fact: First author Shereefa Thekkan initially wanted to make a sensor that would sense superoxide, a reactive oxygen species. It turned out that the sensor she made did not sense superoxide at all, but instead responded to HOCl, a different reactive oxygen species! This turned out to be very useful.
Published October 2018 in Nature Materials
From Giulia Galli: The design and optimization of photoelectrodes for artificial photosynthesis are among the open challenges in developing sustainable solar-to-fuel conversion technologies. In this paper we modeled the interface between electrodes and water and understood what may facilitate chemical reactions at the microscopic scale.
Fun Fact: Although people usually focus on bulk properties, we decided to look at interfaces between the solid and the liquid. We knew it would be much more difficult than a bulk system, but not THAT difficult. We learned a lot in the process and thanks to first author Matteo Gerosa, who never ever gave up, we finished and published a nice story!