Advancing Biology by Bridging Experimental and Computational Sciences

Professor John Rinn has joined the faculty of the University of Colorado in Boulder, to better understand how RNA genes can interact and influence protein gene function. This goal requires high-throughput screening of RNA molecules for those with specific biological activity and creative computational solutions towards understanding the molecular grammar underlying how RNA “speaks” to the cell. Specifically, this requires new training platforms and courses in what is now termed Bioinformatics that seamless blends experimental and computational logic.

Bioinformatics is a new field that blends elements of biology, statistics, computer science, and genetic engineering. It developed as a solution to a major problem: the sheer abundance of data that cannot be analyzed with mechanical devices. Bioinformatics detects data patterns that shed new light on biological processes. With new an emerging applications of machine learning computational methods for deeper insights into big data.

The discipline has streamlined the invention of new treatments for cancer and determined genetic causes for many diseases. Its techniques are well-suited to precision medicine – the customization of medicine to individual circumstances. It also plays a key role in diagnosing and preventing illnesses such as the flu, heart disease, and diabetes.

This growing field has many applications for pharmaceutical companies, software developers and biotechnology. Further evidence of its influence is the fact that more than 45 American colleges and universities now offer degrees in bioinformatics.

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CRISPR-Driven Genetic Alterations Have Significant Implications

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Now teaching at the University of Colorado in Boulder, John Rinn focuses on research into the influence of ribonucleic acid (RNA) on establishing unique cellular states in development and disease. His research focus on the noncoding positions of the human genome, the regions that don’t encode for classic protein coding genes. This requires modifying the human genome in stem cell lines to uncover novel regulatory elements that are required to maintain the pluripotent state or prevent cellular differentiation. This also requires genome modifications that represent those identified in human disease, the vast majority of which reside in the noncoding genome.

The advent of CRISPR technologies turbo-boosted these efforts in several ways. Primarily, with the new throughput and ease of screening thousands of previous unexplored regions of the human genome for biological activity. Also this facilitated developing new tools such as CRISPR-Display that serves as a cellular drone. Where the location and cargo can be specified by specific RNA molecule extensions to CRISPR-CAS9 guide sequences (https://en.wikipedia.org/wiki/CRISPR-Display).

Although CRISPR first caught the public eye in 2018, when a Korean scientist allegedly created HIV-resistant babies, scientists have known about it for nine years. CRISPRs are sequences of genetic material that were first found in bacteria and other microorganisms. They allow these invisible creatures to defend themselves by breaking up pieces of harmful DNA.

Later research has shown that CRISPR’s are found in many forms of life. These versatile molecules can be used to make alterations in DNA much faster and cheaper than previous methods.

These so-called biological machines have several applications. They have been used to vaccinate yogurt against viruses and create crops that can better withstand droughts. It’s thought that one day, CRISPRs could destroy entire populations of mosquitos or bring extinct species back to life.

However, their use raises serious ethical questions about placing them in the human body. The method is imprecise – it could inadvertently damage beneficial DNA. Where do we draw the line between using CRISPRs to cure diseases and enhancing desirable traits? Is it right to make changes without the consent of humans yet to be born?

In response, the National Academies of Sciences, Engineering and Medicine has recommended that CRISPRs be restricted to treating serious diseases that have no other cure. Risks and benefits should be fully publicized and monitored during clinical trials. Finally, research into human side effects should span several generations.

Pioneering Research Efforts at the BioFrontiers Institute

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John Rinn, University of Colorado Boulder

As a doctoral student at Yale University, John Rinn began groundbreaking research in the field of genetics. Following the discovery of a type of RNA known as LINC (large intervening non-coding RNA), John Rinn continued his research as a professor at Harvard University until 2017, when he accepted the Marvin H. Caruthers Endowed Chair for Early-Career Faculty at the BioFrontiers Institute at the University of Colorado Boulder, where he also serves as the Leslie Orgel Professor of RNA Science.

Headed by Nobel Prize recipient Thomas Cech, the BioFrontiers Institute operates under the umbrella of the University of Colorado Boulder. It focuses particularly on cutting-edge research efforts, drawing innovative minds from around the world.

In order to create an environment for its pioneering research, the BioFrontiers Institute encompasses experienced faculty members from a diverse range of academic backgrounds. By bringing together researchers in physical and life sciences as well as professionals in engineering and computer science, the institute encourages exciting collaboration in areas such as genome exploration.

For more information about the BioFrontiers Institute and its current research efforts, visit http://www.colorado.edu/biofrontiers.

Discovery of HOTAIR, FIRRE and other lncRNAs

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A former professor of stem cell and regenerative biology at Harvard University, John Rinn recently became the Marvin H. Caruthers Endowed Chair for Early-Career Faculty at the BioFrontiers Institute at the University of Colorado Boulder, where he is also the Leslie Orgel Professor of RNA Science. While studying for his PhD in molecular biophysics and biochemistry at Yale University, John Rinn discovered that the human genome encoded numerous new RNA genes call long noncoding RNAs or large intervening non-coding RNAs (lincRNA)

Known for its pivotal role in the body along with proteins and DNA (deoxyribonucleic acid), RNA (ribonucleic acid) aids cells in carrying out the genetic code. Scientists have begun to discover more and more types of RNA, revealing its crucial role in the cellular process, a role better likened to director than helper.

One important example of this perspective comes from the discovery of HOTAIR and its functions. Research reveals that the molecule guides the response of the immune system, controls cancer growth, oversees the production of fat and stem cells, and transports proteins to gene clusters, among other activities.

Since this early finding the Rinn laboratory has been working harder to find lncRNA loci that when removed from an animal cause dramatic changes to the animals physiology such or a phenotype. This has lead to the discovery of FIRRE that is required to generate key stem cell populations in the immune system. However, too much FIRRE will over-ride some immune responses leading to death. Thus the FIRRE RNA gene is a new clue into how the human immune system has evolved and functions.

The next step for researchers will be to understand how these lncRNAs function on a molecular level. Once the molecular logic of these mysterious RNA genes in uncovered scientists can begin to explore new avenues for lncRNA therapeutics.

discover the genetic code behind the function of HOTAIR and other LINCs. Further discoveries in this field could provide substantial benefits in terms of improving health and wellness through manipulation of the genome.

The Editorial and Publishing Standards at Genome Biology

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As a HHMI early career scientist, John Rinn dedicates his research to RNA biology. Specifically, focusing on how long noncoding RNA (lncRNA) genes can play important biological roles as RNA molecules (rather than the more commonly studied protein based genes). John Rinn teaches courses at the University of Colorado Boulder as the Leslie Orgel Professor of RNA Science. Outside his basic research, John Rinn also serves on the editorial board of Genome Biology, a leading peer-reviewed, open-access scientific journal.

Genome Biology is committed to publishing exceptional research in all areas of biomedicine and biology studied through a post-genomic and genomic lens. For its work, Thomson Reuters listed Genome Biology the fourth-ranked journal in terms of impact in the Genetics and Heredity category. Here are several editorial and publishing practices at Genome Biology that have contributed to its status within the industry.

1. The journal has more than 46,000 followers on its Twitter account and is dedicated to promoting its content both through its social media presence, well-designed homepage, and press releases.

2. Committed to editorial transparency, Genome Biology publishes a peer reviewer report with every article it publishes. (This practice pertains to submissions starting on January 1, 2019.)

3. To better serve authors, reviewers, and readers, the journal maintains high standards of hospitality throughout the publishing process, including proactive communication on the progress of a manuscript.