Creating collaboration by breaking down scientific barriers.

The scientific world rewards the individual while often discouraging collaboration. However, times of crisis show us how much more we can accomplish when we work together. Here, we describe our approach to breaking down silos and fostering global collaborations and share the lessons we have learned, especially pertaining to research on SARS-CoV-2.

Nurturing Undergraduate Researchers in Biomedical Sciences.

Undergraduate researchers are the next-generation scientists. Here, we call for more attention from our community to the proper training of undergraduates in biomedical research laboratories. By dissecting common pitfalls, we suggest how to better mentor undergraduates and prepare them for flourishing careers.

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.

Africa Needs a New Public Health Order to Tackle Infectious Disease Threats.

The SARS-CoV-2 pandemic has revealed that Africa needs a new public health order to be resilient, to adapt, and to cope with 21st-century disease threats. The new order will need strengthened continental and national public health institutions; local manufacturing of vaccines, therapeutics, and diagnostics; attraction, training, and retention of a public health workforce; and fostering of respectful local and international partnerships.

Postdocs, What Would You Tell Your Younger Self?

Looking back at the time spent in graduate school and postdoctoral training can be illuminating. We asked postdoctoral researchers to tell us what kind of advice they would give to their younger selves.

Going Public in Support of Science.

Scientists are stepping up like never before to support science in the public arena. In big and small ways, scientists are adopting creative ideas to promote science.

Faculty searches get a facelift.

Hiring committees address the glut of highly qualified applicants for faculty positions by experimenting with new evaluation methods and adapting their expectations for today's increasingly competitive academic environment.

Quantifying hierarchy and dynamics in US faculty hiring and retention.

Faculty hiring and retention determine the composition of the US academic workforce and directly shape educational outcomes1, careers2, the development and spread of ideas3 and research priorities4,5. However, hiring and retention are dynamic, reflecting societal and academic priorities, generational turnover and efforts to diversify the professoriate along gender6-8, racial9 and socioeconomic10 lines. A comprehensive study of the structure and dynamics of the US professoriate would elucidate the effects of these efforts and the processes that shape scholarship more broadly. Here we analyse the academic employment and doctoral education of tenure-track faculty at all PhD-granting US universities over the decade 2011-2020, quantifying stark inequalities in faculty production, prestige, retention and gender. Our analyses show universal inequalities in which a small minority of universities supply a large majority of faculty across fields, exacerbated by patterns of attrition and reflecting steep hierarchies of prestige. We identify markedly higher attrition rates among faculty trained outside the United States or employed by their doctoral university. Our results indicate that gains in women's representation over this decade result from demographic turnover and earlier changes made to hiring, and are unlikely to lead to long-term gender parity in most fields. These analyses quantify the dynamics of US faculty hiring and retention, and will support efforts to improve the organization, composition and scholarship of the US academic workforce.

From serendipity to therapy.

My postdoctoral training in the biosynthesis of plant polysaccharides at the University of California, Berkeley, led me, rather improbably, to study mucopolysaccharide storage disorders in the intramural program of the National Institutes of Health (NIH). I have traced the path from studies of mucopolysaccharide turnover in cultured cells to the development of therapy for patients. The key experiment started as an accident, i.e., the mixing of cells of different genotypes, resulting in correction of their biochemical defect. This serendipitous experiment led to identification of the enzyme deficiencies in the Hurler and Hunter syndromes, to an understanding of the biochemistry of lysosomal enzymes in general, and to the cell biology of receptor-mediated endocytosis and targeting to lysosomes. It paved the way for the development of enzyme replacement therapy with recombinant enzymes. I have also included studies performed after I moved to the University of California, Los Angeles (UCLA), including a recent unexpected finding in a neurodegenerative mucopolysaccharide storage disease, the Sanfilippo syndrome, with implications for therapy.

Journey of a molecular biologist.

My journey into a research career began in fermentation biochemistry in an applied science department during the difficult post-World War II time in Japan. Subsequently, my desire to do research in basic science developed. I was fortunate to be a postdoctoral fellow in the United States during the early days of molecular biology. From 1957 to 1960, I worked with three pioneers of molecular biology, Sol Spiegelman, James Watson, and Seymour Benzer. These experiences helped me develop into a basic research scientist. My initial research projects at Osaka University, and subsequently at the University of Wisconsin, Madison, were on the mode of action of colicins as well as on mRNA and ribosomes. Following success in the reconstitution of ribosomal subunits, my efforts focused more on ribosomes, initially on the aspects of structure, function, and in vitro assembly, such as the construction of the 30S subunit assembly map. After this, my laboratory studied the regulation of the synthesis of ribosomes and ribosomal components in Escherichia coli. Our achievements included the discovery of translational feedback regulation of ribosomal protein synthesis and the identification of several repressor ribosomal proteins used in this regulation. In 1984, I moved to the University of California, Irvine, and initiated research on rRNA transcription by RNA polymerase I in the yeast Saccharomyces cerevisiae. The use of yeast genetics combined with biochemistry allowed us to identify genes uniquely involved in rRNA synthesis and to elucidate the mechanism of initiation of transcription. This essay is a reflection on my life as a research scientist.

My life with nature.

After a childhood in Germany and being a youth in Grand Forks, North Dakota, I went to Harvard University, then to graduate school in biochemistry at the University of Wisconsin. Then to Washington University and Stanford University for postdoctoral training in biochemistry and genetics. Then at the University of Wisconsin, as a professor in the Department of Biochemistry and the Department of Genetics, I initiated research on bacterial chemotaxis. Here, I review this research by me and by many, many others up to the present moment. During the past few years, I have been studying chemotaxis and related behavior in animals, namely in Drosophila fruit flies, and some of these results are presented here. My current thinking is described.

scDOT: enhancing single-cell RNA-Seq data annotation and uncovering novel cell types through multi-reference integration.

The proliferation of single-cell RNA-seq data has greatly enhanced our ability to comprehend the intricate nature of diverse tissues. However, accurately annotating cell types in such data, especially when handling multiple reference datasets and identifying novel cell types, remains a significant challenge. To address these issues, we introduce Single Cell annotation based on Distance metric learning and Optimal Transport (scDOT), an innovative cell-type annotation method adept at integrating multiple reference datasets and uncovering previously unseen cell types. scDOT introduces two key innovations. First, by incorporating distance metric learning and optimal transport, it presents a novel optimization framework. This framework effectively learns the predictive power of each reference dataset for new query data and simultaneously establishes a probabilistic mapping between cells in the query data and reference-defined cell types. Secondly, scDOT develops an interpretable scoring system based on the acquired probabilistic mapping, enabling the precise identification of previously unseen cell types within the data. To rigorously assess scDOT's capabilities, we systematically evaluate its performance using two diverse collections of benchmark datasets encompassing various tissues, sequencing technologies and diverse cell types. Our experimental results consistently affirm the superior performance of scDOT in cell-type annotation and the identification of previously unseen cell types. These advancements provide researchers with a potent tool for precise cell-type annotation, ultimately enriching our understanding of complex biological tissues.

The physician scientist: balancing clinical and research duties.

Physician scientists bridge the gap between biomedical research and clinical practice. However, the continuing decrease in number of people who choose this career path poses a threat to the advancement of biomedical science and the translation of research findings to clinical practice.

Predicting molecular properties based on the interpretable graph neural network with multistep focus mechanism.

Graph neural networks based on deep learning methods have been extensively applied to the molecular property prediction because of its powerful feature learning ability and good performance. However, most of them are black boxes and cannot give the reasonable explanation about the underlying prediction mechanisms, which seriously reduce people's trust on the neural network-based prediction models. Here we proposed a novel graph neural network named iteratively focused graph network (IFGN), which can gradually identify the key atoms/groups in the molecule that are closely related to the predicted properties by the multistep focus mechanism. At the same time, the combination of the multistep focus mechanism with visualization can also generate multistep interpretations, thus allowing us to gain a deep understanding of the predictive behaviors of the model. For all studied eight datasets, the IFGN model achieved good prediction performance, indicating that the proposed multistep focus mechanism also can improve the performance of the model obviously besides increasing the interpretability of built model. For researchers to use conveniently, the corresponding website (http://graphadmet.cn/works/IFGN) was also developed and can be used free of charge.

Professional Master of Health Science in Laboratory Medicine: Training Clinical Laboratory Scientists in an Integrated Program at a Research-Intensive University.

A 2-year professional master of health science program at the University of Toronto provides a unique integrated educational program to train allied health science personnel to practice as physician extenders and health care professionals in two high-demand clinical laboratory disciplines, Pathologists' Assistant (PA) and Clinical Embryologist (CE). This report describes an integrated graduate program developed and delivered in a research-intensive laboratory medicine department. The core courses in fundamental biomedical science and in general medical laboratory function and operations formed the foundation on which the requisite clinical skills required to practice as a PA or CE were subsequently delivered as comprehensive CE and PA specialty courses and practicums. Students acquired research skills through courses that teach research methods, critical analysis of research articles, and biostatistics for clinical research scientists. A capstone research project provided students the opportunity to design a research project relevant to the CE or PA fields, perform and analyze the findings, and present the project as an oral abstract and a written scientific article. Students learn to face the clinical challenges by focusing on critical analysis of evidence-based professional practice. The PA field received a 5-year accreditation. CE and PA students presented their clinical research at national and international meetings, with some receiving awards, and published scientific articles. All graduates found meaningful employment in their respective fields, and initial employer response has been favorable.