Premio Nobel de Química 2015 para los padres de los mecanismos de reparación del ADN

La Real Academia de las Ciencias Sueca ha galardonado con el Nobel de Química 2015 a Tomas Lindahl, Paul Modrich y Aziz Sancarr, considerados los padres de los mecanismos de reparación del ADN, cuyo conocimiento ha permitido, por ejemplo, desarrollar tratamientos para enfermedades como el cáncer.

Tomas Lindahl

Prize share: 1/3

Paul Modrich

Prize share: 1/3

Aziz Sancar

Prize share: 1/3

El jurado ha considerado que los trabajos de los tres investigadores han sido clave para aprender cómo reparan las células su ADN y cómo salvaguardan su material genético.

Lindahl (Estocolmo, 1938) trabaja en el Instituto Francis Crick del Reino Unido, Modrich (1946) es investigador de la Universidad de Duke (EEUU) mientras que Sancar (de origen turco, aunque con pasaporte estadounidense) es investigador de la Universidad de Carolina del Norte. Como ha explicado el jurado, nuestras células sufren cada día cientos de alteraciones provocadas por agentes como el tabaco, las radiaciones solares o los radicales libres; "incluso sin esos ataques, el ADN es altamente inestable". Lo que los nuevos Nobel de Química descubrieron en sus laboratorios desde los años 70 es que existe todo un complejo sistema de reparación del material genético de las células para impedir que estos cambios se traduzcan en un completo "caos celular".

El Nobel de Medicina premia nuevos tratamientos contra infecciones de parásitos y malaria

De izquierda a derecha: William C. Campbell, Satoshi Omura y Yoyou Tu

El Nobel de Medicina y Fisiología ha premiado este año avances cruciales contra enfermedades provocadas por parásitos que durante milenios han asolado a la Humanidad y hoy siguen constituyendo uno de los problemas sanitarios más graves del mundo actual, sobre todo en los países más pobres. El Instituto Karolinska ha anunciado en Estocolmo el galardón, que comparten William C. Campbell y Satoshi Omura por descubrir una nueva terapia contra infecciones de lombrices redondas (nemátodos) y Youyou Tu por desarrollar un tratamiento novedoso contra la malaria. Los galardonados compartirán un premio económico de ocho millones de coronas suecas (855.000 euros, 954.000 dólares).

Según informó el comité al dar a conocer el nombre de los galardonados, los tres premiados este año "han desarrollado terapias que han revolucionado el tratamiento de algunas de las más devastadoras enfermedades parasitarias".

El irlandés Campbell y el japonés Omura descubrieron un nuevo fármaco, la Ivermectina, que ha logrado reducir de forma radical la incidencia de la oncocercosis o ceguera de los ríos y la filariasis linfática o elefantiasis, además de mostrar una eficacia parcial contra otras enfermedades parasitarias. La científica china Youyou Tu, por su parte, descubrió la Artemisina, una droga que ha reducido de manera muy significativa la mortalidad por malaria.

Un fármaco 'revolucionario'

El primer compuesto se desarrolló en los años '80 y, según los expertos, rompió todos los esquemas, primero en el mercado veterinario. Mataba parásitos de dos tipos, los que viven en la piel y los que proceden del intestino. Al poco tiempo, este fármaco demostró eficacia contra un parásito 'primo hermano' del que causa la oncocercosis en caballos. Dados los resultados y teniendo en cuenta el grave problema que había en África y Latinoamérica con la ceguera de los ríos en humanos, se pusieron en marcha ensayos clínicos. Se comprobó que en personas, la Ivermectina "no era capaz de matar al parásito (Onchocerca volvulus), pero sí lo dejaba estéril, es decir, conseguía prevenir la enfermedad durante un periodo de tiempo", expone a EL MUNDO Carlos Chaccour, médico e investigador de la Universidad de Navarra.

Desde entonces, como medida de prevención, argumenta Chaccour, "en estas zonas de riesgo, donde la oncocercosis causaba estragos y dejaba a poblaciones enteras ciegas, se toma este fármaco aproximadamente una vez al año. En el Amazonas incluso hasta cuatro veces al año". Tales eran los efectos que la farmacéutica Merck & Co., la empresa que descubrió y fabrica el fármaco, decidió donarlo a los países donde la oncocercosis es endémica. Gracias a ello, se han tratado anualmente a unos 60-80 millones de personas.

La Ivermectina no sólo previene la ceguera de los ríos, también está autorizada en Francia, por ejemplo, para la sarna complicada y actúa frente a otros parásitos como la filariasis linfática o elefantiasis (una enfermedad tropical que puede producir alteraciones del sistema linfático e hipertrofia anormal de algunas partes del cuerpo, causando dolor, discapacidad grave y estigma social), entre otras enfermedades parasitarias.

Tomado de "El Mundo"

Los virus se defienden de nuevo

The battle for survival between bacteria and the viruses that infect them (phages) has led to the evolution of many bacterial defence systems and phage-encoded antagonists of these systems. Clustered regularly interspaced short palindromic repeats (CRISPR) and the CRISPR-associated (cas) genes comprise an adaptive immune system that is one of the most widespread means by which bacteria defend themselves against phages. We identified the first examples of proteins produced by phages that inhibit a CRISPR–Cas system. Here we performed biochemical and in vivo investigations of three of these anti-CRISPR proteins, and show that each inhibits CRISPR–Cas activity through a distinct mechanism. Two block the DNA-binding activity of the CRISPR–Cas complex, yet do this by interacting with different protein subunits, and using steric or non-steric modes of inhibition. The third anti-CRISPR protein operates by binding to the Cas3 helicase–nuclease and preventing its recruitment to the DNA-bound CRISPR–Cas complex. In vivo, this anti-CRISPR can convert the CRISPR–Cas system into a transcriptional repressor, providing the first example—to our knowledge—of modulation of CRISPR–Cas activity by a protein interactor. The diverse sequences and mechanisms of action of these anti-CRISPR proteins imply an independent evolution, and foreshadow the existence of other means by which proteins may alter CRISPR–Cas function.

Tomado de: 

Multiple mechanisms for CRISPR–Cas inhibition by anti-CRISPR protein

Nature

(2015)

doi:10.1038/nature15254

Received

21 November 2014s

Accepted

29 July 2015

Published online

23 September 2015       

Eye-like ocelloids are built from different endosymbiotically acquired components

Multicellularity is often considered a prerequisite for morphological complexity, as seen in the camera-type eyes found in several groups of animals. A notable exception exists in single-celled eukaryotes called dinoflagellates, some of which have an eye-like ‘ocelloid’ consisting of subcellular analogues to a cornea, lens, iris, and retina¹. These planktonic cells are uncultivated and rarely encountered in environmental samples, obscuring the function and evolutionary origin of the ocelloid. Here we show, using a combination of electron microscopy, tomography, isolated-organelle genomics, and single-cell genomics, that ocelloids are built from pre-existing organelles, including a cornea-like layer made of mitochondria and a retinal body made of anastomosing plastids. We find that the retinal body forms the central core of a network of peridinin-type plastids, which in dinoflagellates and their relatives originated through an ancient endosymbiosis with a red alga². As such, the ocelloid is a chimaeric structure, incorporating organelles with different endosymbiotic histories. The anatomical complexity of single-celled organisms may be limited by the components available for differentiation, but the ocelloid shows that pre-existing organelles can be assembled into a structure so complex that it was initially mistaken for a multicellular eye³. Although mitochondria and plastids are acknowledged chiefly for their metabolic roles, they can also be building blocks for greater structural complexity.

a, Illustration of Nematodinium showing the basic components of the ocelloid with their putative organellar origins. b, TEM of the ocelloid of Erythropsidinium, including the lens (L) and retinal body (r). c, TEM of the ocelloid of Nematodinium, depicting the edge of the lens (L) where it is overlain by a cornea-like layer of mitochondria (m). d, Genomic reads amplified from five whole cells of Nematodinium; arrow, retinal body. e, Genomic reads amplified from five retinal bodies (arrow) after they were micro-dissected from individual cells of Nematodinium.

Enlace a la publicación

CRISRP-Cas: una revolución similar a la PCR

Tomado de 

Deep-sea hydrothermal vent bacteria related to human pathogenic Vibrio species

During Alvin and Nautile dives in 1999, samples were collected from water surrounding sulfide chimneys of a hydrothermal vent along the East Pacific Rise and four mesophilic bacteria were isolated, including a novel Vibrio species, Vibrio antiquarius. Genomic, functional, and phylogenetic analyses indicate an intriguing blend of genomic features related to adaptation and animal symbiotic association, and also revealed the presence of virulence genes commonly found in Vibrio species pathogenic for humans. The presence of these virulence genes in an ecologically distinct Vibrio species was surprising. It is concluded that pathogenicity genes serve a far more fundamental ecological role than solely causation of human disease.

Vibrio species are both ubiquitous and abundant in marine coastal waters, estuaries, ocean sediment, and aquaculture settings worldwide. We report here the isolation, characterization, and genome sequence of a novel Vibrio species, Vibrio antiquarius, isolated from a mesophilic bacterial community associated with hydrothermal vents located along the East Pacific Rise, near the southwest coast of Mexico. Genomic and phenotypic analysis revealed V. antiquarius is closely related to pathogenic Vibrio species, namely Vibrio alginolyticus, Vibrio parahaemolyticus, Vibrio harveyi, and Vibrio vulnificus, but sufficiently divergent to warrant a separate species status. The V. antiquarius genome encodes genes and operons with ecological functions relevant to the environment conditions of the deep sea and also harbors factors known to be involved in human disease caused by freshwater, coastal, and brackish water vibrios. The presence of virulence factors in this deep-sea Vibrio species suggests a far more fundamental role of these factors for their bacterial host. Comparative genomics revealed a variety of genomic events that may have provided an important driving force in V. antiquarius evolution, facilitating response to environmental conditions of the deep sea.                          

Enlace al trabajo

                          

Las levaduras pueden producir morfina y opiáceos

Biotechnology is about to make morphine production as simple as brewing beer. A paper published on 18 May in Nature Chemical Biology reports the creation of a yeast strain containing the first half of a biochemical pathway that turns simple sugars into morphine — mimicking the process by which poppies make opiates. Combined with other advances, researchers predict that it will be only a few years — or even months — before a single engineered yeast strain can complete the entire process.

Dueber and colleagues’ work does not reach that goal. But it demonstrates that, given the right genes and biochemical machinery, yeast can convert glucose into the intermediate compound (S)-reticuline — the first half of the poppy’s morphine-production pathway.

Benzylisoquinoline alkaloids (BIAs) are a diverse family of plant-specialized metabolites that include the pharmaceuticals codeine and morphine and their derivatives. Microbial synthesis of BIAs holds promise as an alternative to traditional crop-based manufacturing. Here we demonstrate the production of the key BIA intermediate (S)-reticuline from glucose in Saccharomyces cerevisiae. To aid in this effort, we developed an enzyme-coupled biosensor for the upstream intermediate L-3,4-dihydroxyphenylalanine (L-DOPA). Using this sensor, we identified an active tyrosine hydroxylase and improved its L-DOPA yields by 2.8-fold via PCR mutagenesis. Coexpression of DOPA decarboxylase enabled what is to our knowledge the first demonstration of dopamine production from glucose in yeast, with a 7.4-fold improvement in titer obtained for our best mutant enzyme. We extended this pathway to fully reconstitute the seven-enzyme pathway from L-tyrosine to (S)-reticuline. Future work to improve titers and connect these steps with downstream pathway branches, already demonstrated in S. cerevisiae, will enable low-cost production of many high-value BIAs.

Acceso al trabajo