

In episode one of The Most Unknown, microbiologist Jennifer Macalady, along with a team of divers, spelunk through Italy’s water-rich Frasassi Caves to search for mysterious microbes that could hold clues to the origins of life on Earth. What I really like about the documentary is how it shows science and scientists outside of laboratory and plying their trade in the field, a far cry from the average perspective the public has of modern scientists. This is science at its collaborative best, a look at how seemingly disparate branches and fields are interlinked. The story literally “begins under a mountain, and ends on a monkey island.” The documentary describes itself as an experiment, as it follows each researcher and expert in their respective field, and follows them as they meet and interview the next scientist. The Most Unknown was made possible by the Simons Foundation Science Sandbox. What emerges is a fascinating look at the state of modern science, and a glimpse at where things are headed. The film takes nine scientists for diverse disciplines such as biology and astronomy and catches them all pushing the boundaries of their respective fields into the unknown. We’re talking about The Most Unknown, directed by Peabody-award winning filmmaker Ian Cheney (director of The City Dark and The Search for General Tso) and advised by filmmaker Werner Herzog (known for The Wrath of God and Grizzly Man). It takes viewers on a stunning visual journey into surprising corners of the world and follows along as nine scientists meet for the first time. Watch the Trailer for ‘The Most Unknown,’ Motherboard’s First Feature Documentary The film “The Most Unknown” from Motherboard is both documentary and experiment. “The most intelligent documentary of 2018.” I recently came across a fascinating documentary that not only looks at some of the big questions today in multi-interdisciplinary science, but has scientists ask and interview other scientists. Our results support a model in which uORF coding sequences impact their regulatory functions by altering the speed of uORF translation.All too often, the public perception of science seems to be that we know all that there is to know, and the modern game in science is to simply fill in the gaps in our knowledge. Finally, regression analysis of our results indicated that both codon identity and position impact uORF functions. Inhibitory functions of such uORFs were abrogated by overexpression of complementary tRNA. The presence of rare codons resulted in the most inhibitory uORF variants. Varying uORF codons resulted in a wide range of functions, including both repressor and enhancer uORFs. We investigated the impact of uORF coding regions on their functions by using a massively parallel reporter assay (FACS-uORF) to determine the regulatory functions of thousands of variants of a uORF from the yeast YAP1 gene. Thus, the impact of uORF coding sequences on their regulatory functions remains largely unknown. While a minority of uORFs encode conserved functional peptides, the coding regions of most uORFs are not conserved. Translation of uORFs usually inhibit the translation of downstream main open reading frame (mORF), but some enhance expression.

Upstream Open Reading Frames (uORFs) are important regulatory elements located in 5’ mRNA transcript leaders. Translational regulation plays an important role in eukaryotic gene expression. Yizhu Lin (Department of Biological Sciences, Carnegie Mellon University), Gemma May (Department of Biological Sciences, Carnegie Mellon University), Pieter Spealman (Department of Biological Sciences, Carnegie Mellon University), Lauren Nazzaro (Department of Biological Sciences, Carnegie Mellon University), Hunter Kready (Department of Biological Sciences, Carnegie Mellon University), Joel McManus (Department of Biological Sciences, Carnegie Mellon University) Poster abstracts Poster number 22 submitted by Yizhu Lin Codon usage and position alter the functions of upstream open reading frames
