en News - BIOINFORMATICS BARCELONA News Thu, 07 Nov 2019 09:52:16 +0000 Thu, 07 Nov 2019 09:52:16 +0000 Houdini 2 (http://houdini.antaviana.cat/) http://www.bioinformaticsbarcelona.eu/news The mechanism of the most commonly used antimalarial drugs in near-native conditions unveiled

Plasmodium falciparum parasite, transmitted through mosquito sting, causes the malaria disease infecting red blood cells of its victim. In the last two decades, the parasite has evolved into drug-resistant strains. "Recently, the increasing geographical spread of the species, as well as resistant strains has concerned the scientific community, and in order to improve antimalarial drugs we need to know how they work precisely", explains Sergey Kapishnikov, from the University of Copenhagen in Denmark, and the Weizmann Institute, in Israel, and leader of the study.

Once inside red blood cells, Plasmodium ingests hemoglobin (the protein in charge of oxygen transport) as a nutrient.  After digesting, iron-containing heme molecules are released, which are toxic to the parasite. However, these molecules crystallise into hemozoin, a disposal product formed from the digestion of blood by the parasite that makes the molecules inert. As reported in previous studies, for the parasite to survive, the rate at which the heme molecules are liberated must be slower or the same as the rate of hemozoin crystallization. Otherwise there would be an accumulation of the toxic heme within the parasite.

Quinoline-family drugs, which include quinine-based antimalarial pills, effectively damage the parasite. The scientific community has suspected that the reason for their success is the inability of the heme to crystallise. Until today, all studies of the drug action on heme crystals have been done either on model systems or on dried parasites, which yielded limited data and opened room for speculation. Kapishnikov and his team, which include scientists from Denmark, Spain, Germany, Israel and France, decided to find out the mode of action of established drugs like chloroquine (although they used the analog bromoquine) in fully hydrated, rapidly frozen, Plasmodium falciparum-infected red blood cells. Rapid freezing creates instant snapshots of the living stage of the cells such that chemical distribution therein is unaltered by sample preparation.

Synchrotron complementary techniques

In this case, the same cells maintained under cryogenic conditions had to travel across Europe. The researchers brought them in and out of synchrotron facilities, in order for their structure to be mapped in three dimensions by soft X-ray cryo-tomography at the MISTRAL beamline from the ALBA Synchrotron and BESSY-II in Berlin. This technique, only available in four countries all over the world (UK, USA and these two mentioned in Germany and Spain), is the unique way to image whole cell samples in their native state without any chemical treatment or sectioning.

Finally, cells were brought to ESRF for mapping of bromine and iron distribution by the X-ray fluorescence nano-probe. The synchrotron data were analyzed back in Denmark where scientists determined the correlation between the different imaging modalities and they calculated and interpreted the concentrations of bromoquine at the surface of hemozoin crystals, at the membrane and within the lumen of the parasitic digestive vacuole - the site of the drug action.

The mapped infected red blood cells at the synchrotrons showed that bromoquine caps hemozoin crystals, thereby inhibiting the hemozoin crystal growth and hence, sabotaging heme detoxification. Surprisingly, they also found that bromoquine accumulates in the digestive system of the parasite, which enhances the drug's efficiency in depriving heme from docking onto the hemozoin crystal surface.

"These results show a model that can be generalized to all quinoline drugs, such as quinine, and our approach can be extended to other families of antimalarial drugs, such as artemisinins", explains Kapishnikov. Malaria remains one of the biggest killers in low-income countries, estimates of the number of deaths each year range from 450,000 to 720,000, with the majority of deaths happening in Africa. "We hope that this knowledge will let us go a step further in designing new, effective drugs against resistant malaria strains", he concludes.

IM-MalariaPNAS2

Surface rendering, measured and simulated X-ray fluorescence maps of a bromoquine-treated infected red blood cell (iRBC) labeled A. (A) Surface rendering of a soft X-ray tomography segmentation. (B) Measured iron (Fe) X-ray fluorescence map.(C) Measured brome (Br) X-ray fluorescence map. (D) Simulated Br X-ray fluorescence map. Br atoms were evenly distributed over the surface of the digestive vacuole (DV) membrane, the parasite nucleus, and the parasite membrane with the density of 5·10^3 atoms per μm2, and on the surface of hemozoin (Hz) crystals with a density corresponding to 10% bromoquine surface coverage.


Reference: Sergey KapishnikovTrine StaalsøYang YangJiwoong LeeAna J. Pérez-BernáEva PereiroYang YangStephan WernerPeter GuttmannLeslie Leiserowitz, and Jens Als-Nielsen. Mode of action of quinoline antimalarial drugs in red blood cells infected by Plasmodium falciparum revealed in vivo. PNAS (2019). DOI: 1910123116.

 

]]>
Thu, 07 Nov 2019 09:52:02 +0000 http://www.bioinformaticsbarcelona.eu/news//news/149/the-mechanism-of-the-most-commonly-used-antimalarial-drugs-in-near-native-conditions-unveiled http://www.bioinformaticsbarcelona.eu/news/149 0
Artificial intelligence applied to the diagnosis of rare diseases associated with collagen VI

The system makes the diagnosis from images obtained with a confocal microscope located in the Hospital Sant Joan de Déu Barcelona and is based on artificial learning techniques, using cases previously diagnosed by IRSJD's specialists to generate a fully automatic diagnostic system with a reliability greater than 95%. This valuable tool will allow an objective evaluation of the effectiveness of any new therapy that can be developed to treat these diseases.

Deficiencies in the collagen VI' structure are a common cause of neuromuscular diseases with manifestations ranging from Bethlem myopathy to severe congenital muscular dystrophy Ullrich. Symptoms of these diseases include proximal and axial muscle weakness, distal hyperlaxity, joint contractures and critical respiratory failure that requires assisted ventilation, dramatically reducing life expectancy.

"Although we know that structural defects of collagen VI are related to mutations of the COL6A1, COL6A2 and COL6A3 genes. Diagnosis remains difficult, despite current genetic sequencing technologies." Comment Cecília Jiménez, PhD, research coordinator of the Neuromuscular Diseases Unit.

This difficulty generally occurs in diseases caused by dominant mutations, where there is no complete absence of a major protein, and when the effect of a genetic variant on the protein structure may not be evident. Currently, the diagnosis of dystrophies related to collagen VI is made from the analysis of the images of fibroblast cultures by specialists.

For this analysis, professionals take into account different aspects of the images: the coherence in the orientation of the collagen fibers, the distribution of the collagen network and the disposition of the cells in said network to identify potential patients. However, this evaluation is only qualitative, and regulatory agencies will not approve any treatment (such as genetic editing using CRISPR / Cas9 technology) without an objective methodology to assess its effectiveness.

For this reason, the system proposed in the work published in Applied Soft Computing will be a precise methodology to quantitatively monitor the effects of any new therapy. This system solves, on the one hand, the problem of the lack of data for typical learning in rare diseases; on the other, it indicates the possibly problematic areas in the query images. And it also provides a general quantitative evaluation of the condition of the patients.

Currently, the Neuromuscular Diseases Unit (Institut de Recerca Sant Joan de Déu · Hospital Sant Joan de Déu) is a national and international reference in research and diagnosis of neuromuscular diseases due to collagen deficiency VI.

In the study, researchers from the Neuromuscular Diseases Unit, the Paediatric Neurology Department and the Confocal Microscopy Unit (Daniel Bravo Center for Diagnosis and Research in Minority Diseases and Pediatric Institute of Rare Diseases) collaborated.

The Institute of Robotics and Industrial Informatics is a Joint Research Center of the Spanish Council for Scientific Research (CSIC) and the Technical University of Catalonia (UPC).

Image description: diagnosis display of a fibroblast culture image. The different areas of the image are evaluated independently which allows to quickly identify areas with defects in collagen VI. The system also provides a general diagnosis to track patients.

]]>
Thu, 07 Nov 2019 09:52:16 +0000 http://www.bioinformaticsbarcelona.eu/news//news/147/artificial-intelligence-applied-to-the-diagnosis-of-rare-diseases-associated-with-collagen-vi http://www.bioinformaticsbarcelona.eu/news/147 0
Made of Genes y Synlab presentan "Salud Personalizada: Más allá de la genética"

¿Por qué la dieta que funcionó tan bien a mi compañera de trabajo a mí no me funciona? ¿Por qué me cuesta bajar peso si hago ejercicio? ¿Por qué me afectan tanto los cambios de horario? ¿Por qué si me tomo más de una taza de café no descanso por la noche? ¿Por qué las recomendaciones de estilo de vida son genéricas si yo soy única?

La información genética nos acerca a conocer lo más fundamental de nosotros mismos. Pero la genética no es limitante. Nos permite conocer nuestros límites, sí. Pero también cuál es el mejor camino para romperlos.

Es imprescindible, entonces, conocer no solo cómo eres, sino además cómo estás en cada momento para tener una visión real de nuestras vidas como un punto de partida sobre el que podremos actuar de una u otra manera. Esto es lo que entendemos como salud personalizada.

En este evento moderado por Pere Estupinya (presentador y director de "El ladrón de cerebros" TVE), debatiremos al lado de Dr. Oscar Flores (Doctor en Biomedicina, Ingeniero Informático y cofundador de Made of Genes) y el Dr. David de Lorenzo (experto internacional en Nutrigenómica y Genómica Personal) cómo apoyándonos en la ciencia más innovadora podemos encontrar impactos en la salud que nos permitan educar en estilos de vida saludables personalizados.

 

Fecha y Hora

 

Ubicación

Movistar Centre

16 Plaça de Catalunya

08002 Barcelona

 

]]>
Fri, 13 Sep 2019 12:18:17 +0000 http://www.bioinformaticsbarcelona.eu/news//news/145/made-of-genes-y-synlab-presentan-salud-personalizada-mas-alla-de-la-genetica http://www.bioinformaticsbarcelona.eu/news/145 0
The avocado genome informs deep angiosperm phylogeny

The avocado genome has been sequenced by an international team in which the researchers Julio Rozas and Alejandro Sáncez-Gracia, from the Faculty of Biology and the Biodiversity Research Institute of the UB (IRBio), and members of the platform Bioinformatics Barcelona (BIB) have taken part too.

The new study, published in the journal Proceedings of the National Academy of Science (PNAS), will help improve the programs of genetic modification to optimize the growth of this plant -green gold in the international market- and promote its resistance towards pathogenic agents and diseases, among other aspects.

The study counts on other participants from about twenty institutions, under the supervision of the researchers Luis Herrera-Estrella (Center for Research and Advanced Studies of the National Polytechnic Institute, Mexico), and Víctor A. Albert, from the University of Buffalo (New York, United States).

Avocados, the green gold in worldwide agriculture

People have eaten this tropical fruit from the Persea genera -grown in South America, since pre-Columbian times- a lot over the years, and its consumption has increased worldwide and has generated an economic interest in the international market. The international team has sequenced the genome of two avocado plants, the Mexican variety (Persea americana var. drymifolia) and the most popular culture one (Persea americana Mill. cv. Hass).

The genome of this tropical plant -organized in 12 chromosomes known so far-, has a size of 920 Mb, with little variations among the studied models, according to the new study. "The most relevant element of the genomic structure of the avocado is its history of complete genome duplications", notes Julio Rozas, professor of Genetics and together with Alejandro Sánchez-Gracia, co-director of the Research Group on Evolutionary Genomics and Bioinformatics at the Department of Genetics, Microbiology and Statistics of the UB and IRBio.

In particular, the experts compared the syntenic relationship -the order in which the genes are conserved and positioned in the chromosomes- between the avocado genomes and the species Amborella trichopoda Baill 1869. This species -an endemic plant from New Caledonia- is considered to be the only current representative of the most primitive lineage of flowering plants and angiosperms. In this primitive angiosperm, there are no signs of complete genome duplications, therefore it is the source of the study of genomic duplication evolution for all other flowering plants. 

Tandem duplications and resistance to attacks from pathogens

According to the results, "for one region of the analysed genome, there are four copies of the genomic fragments in the avocado, and one copy in Amborella. This suggests the avocado genome has undergone two complete genome duplication processes", says the researcher Alejandro Sánchez-Gracia (UB-IRBio).    

These recent tandem duplications are involved in adaption metabolic responses of the avocado towards the attack of fungal pathogens, according to the authors. "At the same time, those duplications that appeared during the complete genome duplications -and which are maintained due natural selection- seem to be involved in basic aspects of the plant's development and physiology", notes Sánchez-Gracia.  

Discovering the phylogenetic tree of angiosperm plants

There are still many doubts on the origins and evolution of the avocado plant, a species that belongs to the magnolia genus. The new study profiles a new scenario to find its phylogenetic position in the evolutionary tree of angiosperms, in particular regarding some eudicot species with great economic interest within agriculture, such as coffee (Coffea), or tomato (Solanum), or grapevine (Vitis), which share more genetic compounds among them than with the avocado.  

In this group of plants, the diversification process was fast and it made the phylogenetic analysis difficult. Through a comprehensive phylogenomic analysis of nineteen angiosperm species -with different molecular markers- the new study reveals that the avocado plant is a sibling of the monocotyledon and eudicots families (coffee, tomato, grapevines). 

"The only genetic compounds all these species share are those defining all angiosperms and differentiating from gymnosperms and non-seed plants", notes researcher Pablo Librado, former PhD student of the University of Barcelona and co-author of the study, now member of the Center for Geogenetics of the University of Copenhagen and the Natural History Museum of Denmark. 

From genomic libraries to the Biocomputing software created in the UB

For the sequencing of the Mexican variation, researchers used different genomic libraries and sequencing technology, such as the Bacterial Artificial Cromosome (BAC) or the Illumina platform HiSeq, which provide a great coverage of the studied genome. In Hass, they used the PacBio sequencing methodology (single-molecule real-time-SMRT) with high quality DNA.

The population analysis based on the study of single nucleotide polymorphisms (SNP) enabled getting an insight of the genetic composition and history of the commercial variety Hass, the result of the introgression of genetic material from Guatemala -selective sweeps- in the genomic background of the Mexican avocado.

In the study, the UB-IRBio experts carried out a phylogenomic analysis consisting on the determination of single-copy orthologues and trees with information on aminoacid sequencings and coding nucleotides for this group of genes. A great part of this study was focused on the analysis of the dynamics on the gene loss and origin through BadiRate, a Biocomputing software carried out at the UB by the experts Julio Rozas and Pablo Librado.  

Improving agricultural productivity in world crops

The new study brings a new essential perspective to conduct association studies on the species genome and to find the genes -and different genetic variants- that determine the most relevant features for the economy and productivity of agriculture.  

In this context, the Research Group on Evolutionary Genomics and Bioinformatics of the UB conducted several scientific collaborations with the team of the lecturer Víctor A. Albert, among which stands out the study that identified genetic changes that enabled the adaption of carnivorous diet in different plants (Nature Ecology & Evolution, 2017), an evolutionary process that has been independently repeated in several species using the same molecular solutions.

The UB-IRBio team of experts had a distinguished participation in the sequencing of the genomes of different organisms such as the tick (Ixodes scapularis), centipede (Strigamia maritima), coffee (Coffea canephora), and the body louse (Pediculus humanus humanus), among others.
 

]]>
Fri, 06 Sep 2019 12:30:32 +0000 http://www.bioinformaticsbarcelona.eu/news//news/143/the-avocado-genome-informs-deep-angiosperm-phylogeny http://www.bioinformaticsbarcelona.eu/news/143 0
Experts sequence the genome of an endemic spider from the Canary Islands

A research team of the Faculty of Biology and the Biodiversity Research Institute (IRBio) of the University of Barcelona has sequenced the genome of the spider Dysdera silvatica Schmidt 1981, an endemic species living in the laurel forests in the islands La Gomera, La Palma, and El Hierro -in the Canary Islands. The new study reveals the first genome sequencing of an arthropod in the Canary Islands, an archipelago with a rich biodiversity regarding endemic species that are distributed around the insular area.

Participants in the new study, published in the journal GigaScience, are the experts Julio Rozas, Miquel Arnedo, José Francisco Sánchez-Herrero, Cristina Frías-López, Paula Escuer, Silvia Hinojosa-Alvarez and Alejandro Sánchez-Gracia (UB-IRBio) and also members of the platform Bioinformatics Barcelona (BIB).

Dysdera sylvatica: a ravening predator in the Canary laurel forests

The Dysdera genus, which belongs to the species Dysdera silvatica, includes more than 250 spider species mainly distributed around the Mediterranean area. The Macaronesian archipelagos represent the western limits of the distribution of this taxon, which reached a significant diversification in the Canary Islands, where there are about 50 endemic species currently.

"One of these species is Dysdera silvatica, integrated in an evolutionary lineage that became one of the main predators -both in abundance and diversity- in the insular terrestrial invertebrate trophic networks", notes Professor Miquel Arnedo, from the Department of Evolutionary Biology, Ecology and Environmental Sciences of the Faculty of Biology and the Biodiversity Research Institute (IRBio) of the UB. 

"The species D. silvatica is a generalist predator. Unlike other spider groups, the Dysdera includes experts on hunting and consumption of terrestrial isopods. All these species live in the Canary Islands, where the crustacean trophic specialization seems to have evolved independently several times", adds the researcher, head of the research group on Arthropod Systematics and Animal Evolution of the UB.

The first genome sequencing in the Dysderoidea superfamily

This is the first sequencing of the nuclear and mitochondrial genome for a species of the Dysderoidea superfamily, and the second one known in the Synspermiata group, one of the main spider lineages. Regarding this group, the first species with the available genomic data was the brown recluse spider (Loxoceles reclusa Gertsch & Mulaik, 1940), a species distributed around the American continent and quite known for its necrotic venom. 

According to the conclusions, the genome of the D. silvatica species is large (1.7 Gb) and shows a high complexity, with a high fraction of repetitive elements. According to Professor Julio Rozas (UB-IRBio), who co-led the study together with Alejandro Sánchez-Garcia, "Within this study, we created a 1.4 Gb genomic sequencing assembly, 54 % of which is built by repetitive elements"

"We identified and characterized a total of 36,000 protein-coding gens", notes Professor Julio Rozas (UB-IRBio), head of the research group on Evolutionary Genomics and Bioinformatics at the UB.

The D. silvatica species has a diploid chromosome set of six pairs of autosomes and two (females are XX) or one (males are X0) sex chromosomes (XX-X0), females have six non-sexual chromosome pairs (autosomes) and the XX sexual paired chromosomes. Males have six pairs of autosomes and only one X sexual chromosome. 

Third generation sequencing techniques to treat a complex genome

The research study to sequence the genome of Dysdera silvatica started about five years ago with the application of next generation massive sequencing (NGS) such as Illumina. With this protocol, they created one billion short sequences (100 paired bases) that were not enough to get a quality assembly for the complex genome of the species.

Therefore, the research team completed these data with PacBio and Nanopore single molecule sequencing (SMS) techniques, "more expensive but more efficient methodologies to obtain larger genome sequencing, and provide a quality genomic assembly using the hybrid assembly strategy, combining data from the obtained sequencing through different technologies", notes José Francisco Sánchez-Herrero, member of the Department of Genetics, Microbiology and Statistics of IRBio and first author of the article.

Ecology, evolution and reproductive behavior

From a global perspective, the study brings new views to know more about the genetic bases of the eco-phenotype change that takes place during the adaptive radiation phenomena over biological evolution. In particular, the models from the Dysdera genus in the Canary Islands, the genome sequencing of this first species can bring valuable information on the underlying genetic architecture in the phenotype and physiological changes related to the trophic specialization, as well as the underground environment adaptations, a natural environment where some species got used to live exclusively in the lava tubes.

Regarding their reproductive behavior, the Dysderidae family includes species that show a cryptic female choice mechanism, that is, a reproductive strategy which consists on the female's post-copulatory choice of a male's sperm to fertilize their ova. This choice is conducted through a complex system of diverticulum and glands associated with the female vulva. Knowing the features of the genome of a species from this family could contribute to determine the genetic bases of this behavior, through a comparative study of several regions of the genome under different selective constrictions between sexes, and among species with different sexual strategies.

Last, the study provides useful resources to treat studies on other evolutionary and essential issues, such as the origins and evolution of products with medical and commercial interests produced by spiders (venom, silk, etc.).

]]>
Fri, 06 Sep 2019 12:30:42 +0000 http://www.bioinformaticsbarcelona.eu/news//news/141/experts-sequence-the-genome-of-an-endemic-spider-from-the-canary-islands http://www.bioinformaticsbarcelona.eu/news/141 0
A webserver to study the protein networks perturbed in diseases

Researchers from the UPF, IMIM and UVIC have developed the website GUILDify to study the molecular environment of the proteins involved in diseases. The website is a promising tool to study the molecular mechanisms underlying a disease, to understand the relationships between two diseases and to propose potential drugs for their treatment.

The website GUILDify has been developed at the Structural Bioinformatics Group of GRIB (IMIM-UPF) led by Prof. Baldo Oliva with the objective to study the protein interactions involved in a disease. When accessing the website, the user finds an input box to introduce any disease name and the species of the interactome (human, mouse, rat...). After introducing the disease, GUILDify provides the user with a list of proteins whose corresponding genes are likely to be mutated when the disease occurs. The gene mutations are obtained from DisGeNET, a database of genes associated to human diseases. GUILDify uses these proteins as seeds for an algorithm that searches for the proteins in the interactome that are more connected to them. In the end, the user obtains the protein interactions that are more likely to cause the disease and a list of the biological functions affected.

Quim Aguirre, PhD student at the Structural Bioinformatics Group (SBI) of GRIB, behind this project, tells us all about it in an article on the El·lipse website.

 

]]>
Mon, 17 Jun 2019 10:23:05 +0000 http://www.bioinformaticsbarcelona.eu/news//news/139/a-webserver-to-study-the-protein-networks-perturbed-in-diseases http://www.bioinformaticsbarcelona.eu/news/139 0
Computational method increases design efficiency of protein-based drugs

Researchers from the Institute of Biotechnology and Biomedicine (IBB), in collaboration with scientists from the University of Warsaw recently presented an important update to their AGGRESCAN 3D computational method, focused on facilitating and reducing the cost of developing new generation protein-based drugs, diminishing their propensity to form aggregates and keeping them stable and active for a longer period of time.

Protein aggregation is a common phenomenon found in a wide range of pathologies, from Parkinson's and Alzheimer's diseases to some cancers and type 2 diabetes. A growing molecular knowledge of this phenomenon has yielded the development of different algorithms capable of identifying and predicting the regions with a greater tendency to aggregate. Among the first was AGGRESCAN, developed by the same researchers of the IBB, which took into account the propensity of the linear sequence, but not the 3D structure acquired by globular proteins. Four years ago, this same team of researchers expressed the idea of conducting predictions on these protein structures by implementing the AGGRESCAN 3D (A3D) server. This server offered a higher precision than those based on linear sequencing to predict the aggregation properties of globular proteins. It also provided new features, such as the possibility of easily modelling pathogenic mutations, or a dynamic mode, which allowed modelling the flexibility of small proteins to find potentially hidden regions.

The latest update was presented as a web server freely accessible to the academic world, in addition to a desktop version compatible with Windows, MacOS and Linux. The new algorithm surpasses all previous limitations and substantially broadens computational costs to allow modelling the flexibility of molecules of biomedical interest. It also includes different tools such as an automatic generation of mutations to facilitate redesigns of proteins as antibodies to make them stable and at the same time more soluble, and an improved user interface with which to view the data directly on the website.

"With this update, the A3D becomes one of the most complete aggregation predictors. The fact that one same place offers you the chance to make protein aggregation predictions, model their flexibility, study options for a smart redesign and verify how different factors can affect them, represents a giant step forward with regard to other similar servers", affirms Salvador Ventura, researcher at the IBB and the Department of Biochemistry and Molecular Biology, as well as creator of the A3D. "Among other things, all of this will allow us to improve the production of protein-based drugs, reducing the costs of development, production, storage and distribution".

Protein aggregation, a key element in biomedicine and biotechnology

Protein aggregation has gone from being an ignored area of protein chemistry to becoming a key element within the biomedicine and biotechnology fields. "A bad protein folding and subsequent aggregation is behind a growing number of human disorders and one of the most important impediments to designing and manufacturing proteins for therapeutic applications. These therapies, which imply the use of monoclonal antibodies, growth factors and enzyme substitutions, have already demonstrated high precision of molecular targeting, and therefore the need to study them more in depth becomes even more transcendent", Salvador Ventura concludes.

 

Articles: 
Aleksander Kuriata, Valentín Iglesias, Jordi Pujols, Mateusz Kurcinski, Sebastian Kmiecik and Salvador Ventura. Aggrescan3D (A3D) 2.0: prediction and engineering of protein solubility  Nucleic Acids Research, gkz321, doi.org/10.1093/nar/gkz321
https://academic.oup.com/nar/advance-article/doi/10.1093/nar/gkz321/5485072 

Aleksander Kuriata, Valentín Iglesias, Salvador Ventura and Sebastian Kmiecik. Aggrescan3D standalone package for structure-based prediction of protein aggregation propertiesBioinformatics. 2019 pii: btz143. doi: 10.1093/bioinformatics/btz143.
https://academic.oup.com/bioinformatics/advance-article-abstract/doi/10.1093/bioinformatics/btz143/5368526?redirectedFrom=fulltext

To learn more about how AGGRESCAN3D works please visit the following website: http://biocomp.chem.uw.edu.pl/A3D2/

]]>
Tue, 28 May 2019 07:43:23 +0000 http://www.bioinformaticsbarcelona.eu/news//news/137/computational-method-increases-design-efficiency-of-protein-based-drugs http://www.bioinformaticsbarcelona.eu/news/137 0
First stable simulations of DNA crystals

A research team has presented the first stable simulations of DNA crystals, according to a study published in the journal Chem -part of the publisher Cell- and led by Modesto Orozco, Professor from the Department of Biochemistry and Molecular Biomedicine of the Faculty of Biology of the UB, and head of a research group of the Institute for Research in Biomedicine (IRB Barcelona) and the platform Bioinformatics Barcelona (BIB).

The new study shows the most detailed description so far about the properties of crystal systems with DNA at an atomic scale. This scientific milestone enables explaining the importance of chemical additives which are experimentally used to reach suitable crystallization conditions to get stable crystals in the laboratories.

According to Pablo D. Dans, postdoctoral researcher at IRB Barcelona, "the first to benefit from the study is the community of computational physicists and the chemists and biophysicists, who now have a clear protocol and reference to get stable simulations of DNA crystals".

According to Professor Modesto Orozco, head of the Molecular Modelling and Bioinformatics laboratory of IRB Barcelona, "in the long run, the simulation of several crystals obtained in under different experimental conditions should allow us to predict the effect of a certain chemical additive, and guide crystallographers in their experiments, reducing the costs and the time to get the crystals". 
 


Further information
 

]]>
Thu, 30 May 2019 09:01:19 +0000 http://www.bioinformaticsbarcelona.eu/news//news/135/first-stable-simulations-of-dna-crystals http://www.bioinformaticsbarcelona.eu/news/135 0
Researchers discover the action mechanism of an antitumor drug to treat glioblastoma Glioblastoma is a type of brain tumor with no cure, usually associated with mutations in the epidermal growth factor receptor (EGFR). The main EGFR mutation found in this tumor -known as EGFRvlll- is treated with the antibody mAb806, a drug developed by the Ludwig Institute for Cancer Research (United States) about twenty years ago, although its action mechanism was unknown. Now, a new study published in the journal Proceedings of the National Academy of Science (PNAS) reveals for the first time -the action mechanism of this antibody on the mutated EGFR receptor.

 

The results of the study, which open new pathways for the treatment of cancer, suggest the antibody mAb806 could be used in many tumours in which EGFR has mutated and not only in a specific mutation -like researchers believed so far. The study counts on the participation of experts from the University of Barcelona, the Institute for Research in Biomedicine (IRB Barcelona), Stockholm University (Sweden), and the University of California (United States), among other institutions.


Moreover, the scientific team proved that, even if EGFR has not mutated yet, it can be treated to make it sensitive to the protocol with the antibody mAb806. "These findings provide the rational basis to conduct anti-EGFR therapies combined with antibodies and kinase inhibitors, instead of blind testing them, as it has happened so far", notes Modesto Orozco, professor at the Department of Biochemistry and Molecular Biology at the Faculty of Chemistry of the UB, head of the Molecular Modelling and Bioinformatics Lab at IRB Barcelona and member of the Bioinformatics Barcelona platform (BIB).

 

Further information

 

]]>
Thu, 23 May 2019 09:19:11 +0000 http://www.bioinformaticsbarcelona.eu/news//news/133/researchers-discover-the-action-mechanism-of-an-antitumor-drug-to-treat-glioblastoma http://www.bioinformaticsbarcelona.eu/news/133 0
Ready, set, go for crossing the barrier!

Genes contain all the information needed for the functioning of cells, tissues, and organs in our body. Gene expression, meaning when and how are the genes being read and executed, is thoroughly regulated like an assembly line with several things happening one after another.

Researchers at the Centre for Genomic Regulation (CRG) in collaboration with the Structural Bioinformatics group of GRIB (IMIM-UPF) led by Baldo Oliva and the Department of Molecular Epigenetics, Helmholtz Center Munich, Germany, have discovered a new step in this line, which controls the expression of some genes with an important role in cancer. "We observed that breast cancer cells need a particular modification to express a set of genes required for cellular proliferation and tumour progression," explains the CRG - Beatriu de Pinós postdoctoral researcher Priyanka Sharma, first author of the paper. "This modification allows the enzyme RNA polymerase II to overcome a pausing barrier and to continue to transcribe these genes," adds Sharma.

Cancer cells are willing to quickly proliferate so, genes involved in cell division and proliferation are really active and usually highly expressed. Such a precise and meticulous machinery involves many different molecules to properly function. In this case, when all the machinery to express proliferation genes is ready, it still has to wait for a particular modification to go. As in race when runners are asked to be ready, set and go. Here, the polymerase is also ready and set but still needs a final modification to cross the barrier for transcription and go.

Deciphering every single step and all actors involved in this process is an important achievement in terms of fundamental science. We are now able to better understand how an intricate mechanism of gene regulation actually works and this might be a new target for clinical researchers to study novel therapies for certain types of cancer," states Miguel Beato, CRG group leader and principal investigator in this work.

The work, which has been published in Molecular Cell, describes a novel modification of in the Carboxyl terminal domain of RNA Polymerase II, namely the de-imination of an arginine, by the enzyme PADI2, which allows the polymerase to transcribe genes relevant for cancer cell growth. "Most chemo-therapies are oriented at blocking the activity of enzymes, but we know that PADI2 participates in many different processes involving the nervous system, immune response and inflammation, among others. Thus, inhibiting PADI2 would have multiple side effects. Our results make it possible to target just the particular action of PADI2 on RNA polymerase needed for tumour progression without globally blocking the enzyme," explains Beato.

Reference article: Priyanka Sharma et al. "Arginine citrullination at the c-terminal domain controls RNA polymerase II transcription" Molecular Cell (2018) DOI: 10.1016/j.molcel.2018.10.01.

For further information and media requests, please, contact: Laia Cendrós, press officer, Centre for Genomic Regulation (CRG) - Tel. +34 93 316 0237. For press releases in spanish and catalan click here.

]]>
Mon, 28 Jan 2019 13:00:20 +0000 http://www.bioinformaticsbarcelona.eu/news//news/125/ready-set-go-for-crossing-the-barrier http://www.bioinformaticsbarcelona.eu/news/125 0