Flipons: The Discovery of Z-DNA and Soft-Wired Genomes

Flipons book cover

Flipons

Author(s): Alan Herbert (Author)

  • Publisher: CRC Press
  • Publication Date: March 27, 2024
  • Edition: 1st
  • Language: English
  • Print length: 228 pages
  • ISBN-10: 1032731087
  • ISBN-13: 9781032731087

Book Description

Alan Herbert has played a leading part in discovering the biological roles for a high-energy form of DNA twisted to the left rather than to the right. Both Z-DNA and the Z-RNA sensing proteins are critical for protecting hosts against both viruses and cancers. The proteins also play critical roles in the programmed cell death of aging cells. Other types of flipons exist and alter the readout of transcripts from the genome, encoding genetic information by their shape rather than by their sequence. Many of these flipons are within repeat elements that were previously considered to be just genomic junk. Instead these genetic elements increase the adaptability of cells by flipping DNA conformation. By acting as digital switches, the different flipon types can alter cellular responses without any change to their sequence or any damage to DNA. These highly dynamic structures enable the rapid evolution of multicellular organisms. The junk DNA in repeats also encode peptide patches that enable the assembly of cellular machines. The intransitive logic involved enhances the chance of an individual surviving a constantly changing environment.

Key Features

  • Causes us to rethink how information is encoded in the genome
  • Changes our understanding of how our genome evolved and how we protect ourselves against viruses and cancers while sparing normal cells
  • Shows that high energy forms of DNA, such as left-handed DNA do exist inside the cell
  • Accessible to those in academia and the general public, and speaks to the next generation, encouraging them to find their own path in scientific discovery

The Open Access version of this book, available at http://www.taylorfrancis.com, has been made available under a Creative Commons Attribution-Non-Commercial-No Derivative License (CC-BY-NC-ND) 4.0 license.

Editorial Reviews

From the Author

This book is rather eclectic . It is written by someone in the front trenches during a period when our concepts  changed from a DNA-centric  world view to one where unimagined roles emerged  for RNA and the unconventional  encoding of  information by low complexity repeat regions of DNA. I try to capture the personalities involved and the struggle to overcome the "right" thinking world - yes there are a lot of puns in the book as it describes the discovery underlying the  hugely important  roles played by left-handed DNA in biology.. My career bridges the gap between the low tech bench-top experiments I started with and  AI approaches I now use to analyze the massive troves of data generated by  industrial approaches to unlocking the biology of the cell.. I also give a perspective on the science practiced at institutions like MIT and Merck - both playing critical roles in advancing health care. No book on science would be complete without  a few comments about journal editors and the role they play - both positive and negative - in the role out of scientific advances. A useful update to the history of molecular biology as we move to the  world of RNA therapeutics. I also give my answer to the question of "Why choose a career in science?"

About the Author

Dr. Alan Herbert's career spans both academia and industry. He is Head of Discovery at InsideOutBio and has published in high profile journals. His work on left-handed Z-DNA and Z-RNA has proven that besides the right-handed DNA double helix that Watson and Crick first described, higher energy forms of DNA and RNA are used in the cell to regulate many important biological functions including defenses against viruses and cancer and to regulate the readout of information from the genome. His publications include one providing the first genetic evidence for the biological relevance of the Z-DNA/Z-RNA conformation. This work started with his discovery at MIT of the Zα family of proteins that recognize a form of left-handed DNA called Z-DNA. During this time, Dr. Herbert has had many fruitful collaborations with scientists worldwide who have made great contributions to the work. These discoveries led to the therapeutic targeting of ZBP1lated to develop a new therapy for the treatment of solid tumors. In other endeavors, he pioneered the use of Genome Wide Association Studies at Boston University and contributed to the development of new drug programs at Merck. Dr. Herbert has also helped expand understanding of the role of the alternative DNA structures encoded by genetic elements called flipons in evolution. He has also detailed mechanisms by which the interactions between small noncoding RNAs and flipons regulate the sequence-specific read of genes during embryonic development.

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