Category Archives: Transhuman News

A quest to unravel the architecture of the double helix is revealing the subtle genetic orchestration of life

The genome packs into the nucleus in a manner consistent with the structure of a fractal globule, shown herea polymer state that is extraordinarily dense, but entirely unknotted. Credit: Olena Shmahalo/Quanta Magazine. Globule courtesy Miriam Huntley, Rob Scharein, and Erez Lieberman Aiden

FromQuanta Magazine(findoriginal story here).

The nuclei from a half-million human cells could all fit inside a single poppy seed. Yet within each and every nucleus resides genomic machinery that is incredibly vast, at least from a molecular point of view. It has billions of parts, many used to activate and silence genesan arrangementthat allows individual cells to specialize as brain cells, heart cells and some 200 other different cell types. Whats more, each cells genome is atwitter with millions of mobile pieces that swarm throughout the nucleus and latch on here and there to tweak the genetic program. Every so often, the genomic machinereplicates itself.

At the heart of the human genomes Lilliputian machinery is the two meters worth of DNA that it takes to embody a persons 3 billion genetic letters, or nucleotides. Stretch out all of the genomes in all of your bodys trillions of cells, saysTom Misteli, the head of the cell biology of genomes group at the National Cancer Institute in Bethesda, Md., and it would make 50 round trips to the sun. Since 1953, when James Watson and Francis Crick revealed the structure of DNA, researchers have made spectacular progress in spelling out these genetic letters. But this information-storage view reveals almost nothing about what makes specific genes turn on or off at different times, in different tissue types, at different moments in a persons day or life.

To figure out these processes, we must understand how those genetic letters collectively spiral about, coil, pinch off into loops, aggregate into domains and globules, and otherwise assume a nucleus-wide architecture. The beauty of DNA made people forget about the genomes larger-scale structure, saidJob Dekker, a molecular biologist at the University of Massachusetts Medical School in Worcester who has built some of the most consequential tools for unveiling genomic geometry. Now we are going back to studying the structure of the genome because we realize that the three-dimensional architecture of DNA will tell us how cells actually use the information. Everything in the genome only makes sense in 3-D.

Genome archaeologists like Dekker have invented and deployed molecular excavation techniques for uncovering the genomes architecture with the hope of finally discerning how all of that structure helps to orchestrate life on Earth. For the past decade or so, they have been exposing a nested hierarchy of structural motifs in genomes that are every bit as elemental to the identity and activity of each cell as the double helix.

A better genetic microscope A close investigation of the genomic machine has been a long time in coming. The early British microscopist Robert Hooke coined the wordcellas a result of his mid-17th-century observations of a thin section of cork. The small compartments he saw reminded him of monks living quarterstheir cells. By 1710, Antonie van Leeuwenhoek had spied tiny compartments within cells, though it was Robert Brown, of Brownian motion fame, who coined the wordnucleusto describe these compartments in the early 1830s. A half-century later, in 1888, the German anatomist Heinrich Wilhelm Gottfried von Waldeyer-Hartz peered through his microscope and decided to use the wordchromosomemeaning color bodyfor the tiny, dye-absorbing threads that he and others could see inside nuclei with the best microscopes of their day.

During the 20th century, biologists found that the DNA in chromosomes, rather than their protein components, is the molecular incarnation of genetic information. The sum total of the DNA contained in the 23 pairs of chromosomes is the genome. But how these chromosomes fit together largely remained a mystery.

Then in the early 1990s, Katherine Cullen and a team at Vanderbilt University developed a method to artificially fuse pieces of DNA that are nearby in the nucleusa seminal feat that made it possible to analyze the ultrafolded structure of DNA merely by reading the DNA sequence. This approach has been improved over the years. One of its latest iterations, calledHi-C, makes it possible to map the folding of entire genomes.

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Human Genome's Spirals, Loops and Globules Come into 4-D View [Video]

PRESS RELEASE: Second Genome and Evotec to collaborate in microbiome discovery and development

DGAP-News: Evotec AG / Key word(s): Miscellaneous Second Genome and Evotec to collaborate in microbiome discovery and development

2015-03-13 / 07:31

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Hamburg, Germany - 13 March 2015: Evotec AG (Frankfurt Stock Exchange: EVT, TecDAX, ISIN: DE0005664809) and Second Genome, Inc. today announced a collaboration in small molecule-based discovery and development activities for the treatment of microbiome-mediated diseases. The collaboration comprises the identification and optimisation of novel compounds as well as licence agreements for already existing assets developed by Evotec. Second Genome's unique approach to identify and modulate microbiome-mediated pathways will be further enhanced by the use and the results of Evotec's integrated drug discovery platform.

As part of the collaboration, Second Genome and Evotec will work together to screen microbiome-mediated targets of interest identified by the Second Genome microbiome discovery platform with Evotec's technology platform, chemical libraries and other pre-clinical capabilities. The agreement between Evotec and Second Genome triggers an undisclosed upfront payment. Evotec is also eligible for pre-clinical, clinical and regulatory milestones as well as royalty payments related to commercialisation.

Dr Cord Dohrmann, Chief Scientific Officer of Evotec, commented: "We are pleased to contribute to Second Genome's unique approach to treat microbiome-mediated diseases in the body with a particular emphasis on the gut. The enrichment and maturation of Second Genome's project portfolio through our contributions will enhance the Company's clinical pipeline in the near future."

Mohan Iyer, Chief Business Officer of Second Genome, added: "The partnership with Evotec allows us efficiently to translate our unique microbiome discovery platform efficiently into tangible drug molecules for clinical development. Our enriched pipeline offers new treatment approaches for patients across a wide range of diseases with an initial focus on inflammatory conditions. We look forward to a sustained partnership with Evotec."

Further financial terms were not disclosed.

ABOUT EVOTEC AG Evotec is a drug discovery alliance and development partnership company focused on rapidly progressing innovative product approaches with leading pharmaceutical and biotechnology companies, academics, patient advocacy groups and venture capitalists. We operate worldwide providing the highest quality stand-alone and integrated drug discovery solutions, covering all activities from target-to-clinic. The Company has established a unique position by assembling top-class scientific experts and integrating state-of-the-art technologies as well as substantial experience and expertise in key therapeutic areas including neuroscience, pain, metabolic diseases as well as oncology, inflammation and infectious diseases. Evotec has long-term discovery alliances with partners including Bayer, Boehringer Ingelheim, CHDI, Genentech, Janssen Pharmaceuticals, MedImmune/AstraZeneca, Roche and UCB. In addition, the Company has existing development partnerships and product candidates both in clinical and pre-clinical development. These include partnerships with Boehringer Ingelheim and MedImmune in the field of diabetes, with Janssen Pharmaceuticals in the field of depression and with Roche in the field of Alzheimer's disease. For additional information please go to http://www.evotec.com.

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PRESS RELEASE: Second Genome and Evotec to collaborate in microbiome discovery and development