Led by the College Transition Collaborative and the IU Equity Accelerator, the research team offered a brief online reading and writing exercise to nearly 27,000 students from 22 diverse colleges and universities across the United States in fall 2015 and 2016, including IU. These results, the country’s largest multi-site randomized controlled trial of this belonging intervention, were published May 5 in Science.

“There are hundreds of thousands of students being left behind and not supported by institutions in the way they need to be supported,” said IU Equity Accelerator founder Mary Murphy, professor of psychological and brain sciences and Class of 1948 Herman B Wells Endowed Professor in the IU Bloomington College of Arts and Sciences. “The Equity Accelerator is helping institutions understand what they can do to help students feel like they belong, that they are supported academically.

“It is important that students never feel alone, and that the institution offers tangible affordances that are recognized and used by students to help them feel a sense of belonging and to be academically successful in college.”

The researchers found significant effects on students’ persistence, course taking and sense of belonging after engaging with the reading and writing exercise. The intervention increased the rate at which students completed their first year of college as full-time students, especially among students in groups that had historically progressed at lower rates. However, across the 22 institutions, the impacts were much greater when the institutions had strategies and resources in place to help students feel like they belong.

The researchers have calculated that their results can be generalized to more than 1 million students annually at 749 four-year colleges and universities in the United States, where the 12-month drop-out rate for first-time undergraduate freshmen is 24.1 percent, according to the Education Data Initiative. If all schools in the generalizability sample implemented the online social-belonging intervention, 12,136 more full-time students would complete the first year of college each year. The benefits are greatest among historically lower-performing groups — students whose combined race/ethnicity and generation status is historically lower performing at a particular institution — which helps to reduce inequality on campuses.

The social-belonging intervention was delivered through an online module in the summer before students began college, typically as part of a pre-semester checklist of necessary forms and requirements. It included survey results from older students showing that everyday worries about belonging are normal in the transition to college and can improve over time; carefully curated stories from older students describing these worries and how they improved from them; and an opportunity to reflect on these stories in writing.

Results varied across the 22 institutions, since each offers different strategies, resources and programs to support the particular groups of students who historically struggle with first-year college completion. The researchers say institutional transformation and increasing support for students on campus — as well as students’ knowledge of, attitudes about and usage of these resources — are critical to improving student success.

“This work is globally reimagining the role of institutions on student outcomes, not just from an academic perspective but also students’ life outcomes,” said Sara Woodruff, chief strategy officer at the IU Equity Accelerator. “This is a call to action for the ways in which institutions take their power and use it to really move students. Through the Equity Accelerator, we’re helping institutions reexamine the contract they are creating with students, helping them call out inequities that exist and telling them in real, granular terms what they can do to change.”

The IU Equity Accelerator, formed in July 2022, is a focused research organization whose mission is to use and apply social and behavioral science to provide more equitable learning and working environments where everyone can meet their full potential. Institutions nationwide that are working to improve students’ belonging can work with the Equity Accelerator to identify, from their own students’ perspectives, what resources and strategies are needed to facilitate student belonging on campus.

“In addressing equity, it is important to have actionable results that can be used to improve student experiences and outcomes and help them be the people they are meant to be,” Murphy said. “We hope institutions can build on our findings and the work of the IU Equity Accelerator to identify better ways to support their students.”

The advance — which was recently announced in the journal Nature — uses bacteria to combine natural enzymatic reactions with a new-to-nature reaction called the “carbene transfer reaction.” This work could also one day help reduce industrial emissions because it offers sustainable alternatives to chemical manufacturing processes that typically rely on fossil fuels.

“What we showed in this paper is that we can synthesize everything in this reaction — from natural enzymes to carbenes — inside the bacterial cell. All you need to add is sugar and the cells do the rest,” said Jay Keasling, a principal investigator of the study and CEO of the Department of Energy’s Joint BioEnergy Institute (JBEI).

Carbenes are highly reactive carbon-based chemicals that can be used in many different types of reactions. For decades, scientists have wanted to use carbene reactions in the manufacturing of fuels and chemicals, and in drug discovery and synthesis.

But these carbene processes could only be carried out in small batches via test tubes and required expensive chemical substances to drive the reaction.

In the new study, the researchers replaced expensive chemical reactants with natural products that can be produced by an engineered strain of the bacteria Streptomyces. Because the bacteria use sugar to produce chemical products through cellular metabolism, “this work enables us to perform the carbene chemistry without toxic solvents or toxic gases typically used in chemical synthesis,” said first author Jing Huang, a Berkeley Lab postdoctoral researcher in the Keasling Lab. “This biological process is much more environmentally friendly than the way chemicals are synthesized today,” Huang said.

During experiments at JBEI, the researchers observed the engineered bacterium as it metabolized and converted sugars into the carbene precursor and the alkene substrate. The bacterium also expressed an evolved P450 enzyme that used those chemicals to produce cyclopropanes, high-energy molecules that could potentially be used in the sustainable production of novel bioactive compounds and advanced biofuels. “We can now perform these interesting reactions inside the bacterial cell. The cells produce all of the reagents and the cofactors, which means that you can scale this reaction to very large scales” for mass manufacturing, Keasling said.

Recruiting bacteria to synthesize chemicals could also play an integral role in reducing carbon emissions, Huang said. According to other Berkeley Lab researchers, close to 50% of greenhouse gas emissions come from the production of chemicals, iron and steel, and cement. Limiting global warming to 1.5 degrees Celsius above pre-industrial levels will require severely cutting greenhouse gas emissions in half by 2030, says a recent report by the Intergovernmental Panel on Climate Change.

Huang said that while this fully integrated system can be envisioned for a large number of carbene donor molecules and alkene substrates, it is not yet ready for commercialization.

“For every new advance, someone needs to take the first step. And in science, it can take years before you succeed. But you have to keep trying — we can’t afford to give up. I hope our work will inspire others to continue searching for greener, sustainable biomanufacturing solutions,” Huang said.

This work was supported by the DOE Office of Science and DOE Office of Biological and Environmental Research. Additional support was provided by the National Science Foundation.

“The advantage of organoids is that we can intervene in their development and test active substances on them, which allows us to learn more about healthy tissue as well as diseases,” explains Barbara Treutlein, Professor of Quantitative Developmental Biology at the Department of Biosystems Science and Engineering at ETH Zurich in Basel.

To help produce such an atlas, Treutlein, together with researchers from the Universities of Zurich and Basel, has now developed an approach to gather and compile a great deal of information about organoids and their development. The research team applied this approach to the organoids of the human retina, which they derived from stem cells.

Many proteins visible simultaneously

At the heart of the methods the scientists used for their approach was the 4i technology: iterative indirect immunofluorescence imaging. This new imaging technique can visualise several dozen proteins in a thin tissue section at high resolution using fluorescence microscopy. The 4i technology was developed a few years ago by Lucas Pelkmans, a professor at the University of Zurich and coauthor of the study that has just been published in the scientific journal Nature Biotechnology. It is in this study that the researchers applied this method to organoids for the first time.

Typically, researchers use fluorescence microscopy to highlight three proteins in a tissue, each with a different fluorescent dye. For technical reasons, it is not possible to stain more than five proteins at a time. In 4i technology, three dyes are used, but these are washed from the tissue sample after measurements have been taken, and three new proteins are stained. This step was performed 18 times, by a robot, and the process took a total of 18 days. Lastly, a computer merges the individual images into a single microscopy image on which 53 different proteins are visible. They provide information on the function of the individual cell types that make up the retina; for example, rods, cones, and ganglion cells.

The researchers have supplemented this visual information of retinal proteins with information on which genes are read in the individual cells.

High spatial and temporal resolution

The scientists performed all these analyses on organoids that were of different ages and thus at different stages of development. In this way, they were able to create a time series of images and genetic information that describes the entire 39-week development of retinal organoids. “We can use this time series to show how the organoid tissue slowly builds up, where which cell types proliferate and when, and where the synapses are located. The processes are comparable to those of retinal formation during embryonic development,” says Gray Camp, a professor at the University of Basel and a senior author of this study.

The researchers published their image information and more findings on retinal development on a publicly accessible website: EyeSee4is.

Further tissue types planned

So far, the scientists have been studying how a healthy retina develops, but in the future, they hope to deliberately disrupt development in retinal organoids with drugs or genetic modifications. “This will give us new insights into diseases such as retinitis pigmentosa, a hereditary condition that causes the retina’s light-sensitive receptors to gradually degenerate and ultimately leads to blindness,” Camp says. The researchers want to find out when this process begins and how it can be stopped.

Treutlein and her colleagues are also working on applying the new detailed mapping approach to other tissue types, such as different sections of the human brain and to various tumour tissues. Step by step, this will create an atlas that provides information on the development of human organoids and tissues.