The beauty and challenges of studying cell biology in diverse organisms.

Cell Reports Editor Shawnna Buttery interviewed Holly Goodson, Wallace Marshall, and Thibaut Brunet at the annual ASCB/EMBO Cell Bio conference. Shawnna asked how non-traditional organisms help us better understand the fundamentals of cell biology. A transcript of the conversation appears below, and the full conversation is available with the article online.

Londa Schiebinger.

Dr. Londa Schiebinger is an international leader on the intersection of sex, gender, and science. In this interview with Cell, she discusses the Gendered Innovations project, the persistent STEM gender gap, the importance of considering sex- and gender-related variables and intersectionality in research, and the future of sex and gender research.

The SkillsCenter: Creating scalable research opportunities for STEM students.

Undergraduate students generally need laboratory skills and experience to be accepted into a position within an academic lab or a company. However, those settings are traditionally where students would develop that necessary expertise. We developed a laboratory course paradigm to equip students with the skills they need to access future opportunities.

Making glaucoma genetic studies more diverse.

Although the blinding eye disease glaucoma is more common in people of African ancestry, previous genetic studies predominantly involved European subjects. In this issue of Cell, O'Brien et al. report a genome-wide association study for glaucoma in individuals of African ancestry, showing overlap with European studies and refining an African polygenic risk score.

The genetic changes that shaped Neandertals, Denisovans, and modern humans.

Modern human ancestors diverged from the ancestors of Neandertals and Denisovans about 600,000 years ago. Until about 40,000 years ago, these three groups existed in parallel, occasionally met, and exchanged genes. A critical question is why modern humans, and not the other two groups, survived, became numerous, and developed complex cultures. Here, we discuss genetic differences among the groups and some of their functional consequences. As more present-day genome sequences become available from diverse groups, we predict that very few, if any, differences will distinguish all modern humans from all Neandertals and Denisovans. We propose that the genetic basis of what constitutes a modern human is best thought of as a combination of genetic features, where perhaps none of them is present in each and every present-day individual.

Modular pooled discovery of synthetic knockin sequences to program durable cell therapies.

Chronic stimulation can cause T cell dysfunction and limit the efficacy of cellular immunotherapies. Improved methods are required to compare large numbers of synthetic knockin (KI) sequences to reprogram cell functions. Here, we developed modular pooled KI screening (ModPoKI), an adaptable platform for modular construction of DNA KI libraries using barcoded multicistronic adaptors. We built two ModPoKI libraries of 100 transcription factors (TFs) and 129 natural and synthetic surface receptors (SRs). Over 30 ModPoKI screens across human TCR- and CAR-T cells in diverse conditions identified a transcription factor AP4 (TFAP4) construct that enhanced fitness of chronically stimulated CAR-T cells and anti-cancer function in vitro and in vivo. ModPoKI's modularity allowed us to generate an ∼10,000-member library of TF combinations. Non-viral KI of a combined BATF-TFAP4 polycistronic construct enhanced fitness. Overexpressed BATF and TFAP4 co-occupy and regulate key gene targets to reprogram T cell function. ModPoKI facilitates the discovery of complex gene constructs to program cellular functions.

The next big questions in cancer research.

Our understanding of tumorigenesis and cancer progression as well as clinical therapies for different cancer types have evolved dramatically in recent years. However, even with this progress, there are big challenges for scientists and oncologists to tackle, ranging from unpacking the molecular and cellular mechanisms involved to therapeutics and biomarker development to quality of life in the aftermath of therapy. In this article, we asked researchers to comment on the questions that they think are important to address in the coming years.

A uniform format for manuscript submission.

Many scientists spend unnecessary time reformatting papers to submit them to different journals. We propose a uniform submission format that we hope journals will include in their options for submission. Widespread adoption of this uniform submission format could shorten the submission and publishing process, freeing up time for research.

Organs-on-a-chip models for biological research.

We explore the utility of bioengineered human tissues-individually or connected into physiological units-for biological research. While much smaller and simpler than their native counterparts, these tissues are complex enough to approximate distinct tissue phenotypes: molecular, structural, and functional. Unlike organoids, which form spontaneously and recapitulate development, "organs-on-a-chip" are engineered to display some specific functions of whole organs. Looking back, we discuss the key developments of this emerging technology. Thinking forward, we focus on the challenges faced to fully establish, validate, and utilize the fidelity of these models for biological research.

Unrealized potential from smaller institutions: Four strategies for advancing STEM diversity.

Diversity within science, technology, engineering, and mathematics (STEM) remains disturbingly low. Relative to larger, highly funded universities, smaller schools harbor more diverse student demographics and more limited resources. Here, we propose four strategies leveraging the unique advantages of smaller institutions to advance underrepresented scholars along STEM pathways.

Infodemics: A new challenge for public health.

The COVID-19 information epidemic, or "infodemic," demonstrates how unlimited access to information may confuse and influence behaviors during a health emergency. However, the study of infodemics is relatively new, and little is known about their relationship with epidemics management. Here, we discuss unresolved issues and propose research directions to enhance preparedness for future health crises.

How Support of Early Career Researchers Can Reset Science in the Post-COVID19 World.

The COVID19 crisis has magnified the issues plaguing academic science, but it has also provided the scientific establishment with an unprecedented opportunity to reset. Shoring up the foundation of academic science will require a concerted effort between funding agencies, universities, and the public to rethink how we support scientists, with a special emphasis on early career researchers.

Biomedical Research Goes Viral: Dangers and Opportunities.

Researchers around the globe have been mounting, accelerating, and redeploying efforts across disciplines and organizations to tackle the SARS-CoV-2 outbreak. However, humankind continues to be afflicted by numerous other devastating diseases in increasing numbers. Here, we outline considerations and opportunities toward striking a good balance between maintaining and redefining research priorities.

National Efforts with Global Implications.

As genome sequencing at a large scale becomes more and more accessible, national genomics programs are taking off around the world and providing critical insights into our understanding of the human genome. Cell's April Pawluk caught up with Fowzan Alkuraya of the Saudi Human Genome Program and Jianjun Liu of Singapore's SG10K Program to hear about their national efforts, the benefits and challenges to studying their unique local populations, and the future of genomics-led healthcare around the world. Annotated excerpts from this conversation are presented below, and the full conversation is available with the article online.

Diseases Have No Borders, Neither Should Research!

In response to recent anti-Chinese sentiment in the US, Sunney Xie uses his own experiences to assert that American ideals should not be replaced by nationalism and populism and that everybody wins in Sino-US scientific collaborations, contrary to what Americans are led to believe: that China is the sole beneficiary.

Take a Deep Breath and Switch.

Choosing a research topic is an important decision at any level. The choice shapes decisions about what graduate lab to join, which post-doctoral position to pursue, how to start an independent lab, and what companies might make good employers. The thing to remember is that "the choice" can, and perhaps should, be made many times during a career, and each time, it can take an exciting new turn. Lara Szewczak sat down with Amy Gladfelter and Tony Hyman to talk about what it takes for a researcher to pivot-to decide that they want to embark on a new line of research. What does it mean at different points in a career, and how can you motivate colleagues to follow? Annotated excerpts from this conversation are presented below, and the full conversation is available with the article online.

Chasing Histone Biology from Sea Urchins to Yeast.

Together with David Allis, Michael Grunstein just received the Lasker Basic Medical research award. The article that follows is a transcript of a conversation with Jacques Deguine, scientific editor at Cell, that was edited for length. Annotated excerpts from this conversation are presented below, and the full conversation is available with the article online.

Leading and Inspiring by Example.

Joan Steitz radiates a passion for science. Whether she's teaching an undergraduate course, mentoring a grad student or post-doc, or speaking at a scientific conference, her enthusiasm and curiosity for all things RNA is infectious. Joan, the recipient of the 2018 Lasker-Koshland Special Achievement Award in Medical Science, spoke with Cell editor (and her former post-doc) Lara Szewczak about how she came to be an advocate for women in science and shared advice for young scientists entering the research community today. Annotated excerpts from this conversation are presented below, and the full conversation is available with the article online.

Microbiome Research in a Social World.

Should we get our microbiomes sequenced? Do we shape our microbes, or do our microbes shape us? These are just a few of the questions at the border between microbiome science and humanities.

The Human Gut Microbiome: From Association to Modulation.

Our understanding of the human gut microbiome continues to evolve at a rapid pace, but practical application of thisknowledge is still in its infancy. This review discusses the type of studies that will be essential for translating microbiome research into targeted modulations with dedicated benefits for the human host.