Posts tagged biology
Articles and news from the latest research reports.
Stanford researchers produce first complete computer model of an organism
A mammoth effort has produced a complete computational model of the bacterium Mycoplasma genitalium, opening the door for biological computer-aided design.
In a breakthrough effort for computational biology, the world’s first complete computer model of an organism has been completed, Stanford researchers reported last week in the journal Cell.
A team led by Markus Covert, assistant professor of bioengineering, used data from more than 900 scientific papers to account for every molecular interaction that takes place in the life cycle of Mycoplasma genitalium, the world’s smallest free-living bacterium.
By encompassing the entirety of an organism in silico, the paper fulfills a longstanding goal for the field. Not only does the model allow researchers to address questions that aren’t practical to examine otherwise, it represents a stepping-stone toward the use of computer-aided design in bioengineering and medicine.
"This achievement demonstrates a transforming approach to answering questions about fundamental biological processes," said James M. Anderson, director of the National Institutes of Health Division of Program Coordination, Planning and Strategic Initiatives. "Comprehensive computer models of entire cells have the potential to advance our understanding of cellular function and, ultimately, to inform new approaches for the diagnosis and treatment of disease."
The research was partially funded by an NIH Director’s Pioneer Award from the National Institutes of Health Common Fund.
More than 125 years ago, Santiago Ramón y Cajal was able to draft and prove the neuron doctrine, and later, to develop prophetic theories about neural function and plasticity, many of which have been proven by current neuroscience.
It was chance that made Cajal, during his doctorate studies, have his first contact with histology and force him to study the then current theories about pathogenesis of inflammation.
Thus, he gained knowledge of the vascular hypothesis, by Julius Cohnheim, a German pathologist who, opposing the opinion of his teacher and father of cellular pathology, Rudolf Virchow, made leukocytes the protagonists of inflammation, given their ability to develop ameboid movements directed by chemical signals. Cohnheim’s chemotactic theory deeply influenced Cajal’s conception of biology. So, the basic postulates of chemotaxis can be identified at different moments in Cajal’s research, from the description of the “growth cone” in embryonic neuroblasts, the origin of the neurotrophic theory, to the proposal of the pathophysiological mechanisms of neuronal plasticity.
From Cajal’s point of view, the neurons move during their development and also adapt to different external circumstances. Chemical endogenous substances can stimulate this movement in a similar way to leukocytes during the process of inflammation.
Source: Neuroscience, Volume 217, Pages 1-5 (16 August 2012)
Researchers identify mechanisms that allow embryonic stem cells to become any cell in the human body
July 18, 2012
(Phys.org) — New research at the Hebrew University of Jerusalem sheds light on pluripotency—the ability of embryonic stem cells to renew themselves indefinitely and to differentiate into all types of mature cells. Solving this problem, which is a major challenge in modern biology, could expedite the use of embryonic stem cells in cell therapy and regenerative medicine. If scientists can replicate the mechanisms that make pluripotency possible, they could create cells in the laboratory which could be implanted in humans to cure diseases characterized by cell death, such as Alzheimer’s, Parkinson’s, diabetes and other degenerative diseases.
To shed light on these processes, researchers in the lab of Dr. Eran Meshorer, in the Department of Genetics at the Hebrew University’s Alexander Silberman Institute of Life Sciences, are combining molecular, microscopic and genomic approaches. Meshorer’s team is focusing on epigenetic pathways—which cause biological changes without a corresponding change in the DNA sequence—that are specific to embryonic stem cells.
The molecular basis for epigenetic mechanisms is chromatin, which is comprised of a cell’s DNA and structural and regulatory proteins. In groundbreaking research performed by Shai Melcer, a PhD student in the Meshorer lab, the mechanisms which support an “open” chromatin conformation in embryonic stem cells were examined. The researchers found that chromatin is less condensed in embryonic stem cells, allowing them the flexibility or “functional plasticity” to turn into any kind of cell.
A distinct pattern of chemical modifications of chromatin structural proteins (referred to as the acetylation and methylation of histones) enables a looser chromatin configuration in embryonic stem cells. During the early stages of differentiation, this pattern changes to facilitate chromatin compaction.
But even more interestingly, the authors found that a nuclear lamina protein, lamin A, is also a part of the secret. In all differentiated cell types, lamin A binds compacted domains of chromatin and anchors them to the cell’s nuclear envelope. Lamin A is absent from embryonic stem cells and this may enable the freer, more dynamic chromatin state in the cell nucleus. The authors believe that chromatin plasticity is tantamount to functional plasticity since chromatin is made up of DNA that includes all genes and codes for all proteins in any living cell. Understanding the mechanisms that regulate chromatin function will enable intelligent manipulations of embryonic stem cells in the future.
"If we can apply this new understanding about the mechanisms that give embryonic stem cells their plasticity, then we can increase or decrease the dynamics of the proteins that bind DNA and thereby increase or decrease the cells’ differentiation potential," concludes Dr. Meshorer. “This could expedite the use of embryonic stem cells in cell therapy and regenerative medicine, by enabling the creation of cells in the laboratory which could be implanted in humans to cure diseases characterized by cell death, such as Alzheimer’s, Parkinson’s, diabetes and other degenerative diseases.”
Source: PHYS.ORG
Scientists have developed a statistical method using evolutionary information to significantly enhance the likelihood of identifying disease-associated alleles in the genome that show better consistency across populations.
The group’s research appeared in the advanced online issue of the journal Molecular Biology and Evolution. The new method is now available to use via the web, so that researchers worldwide can apply it as an aid to discovering disease-associated mutations that are more consistently reproducible and therefore useable as diagnostic markers. Kumar refers to this new approach, combining standard comparative genomic studies with phylogenetic data as phylomedicine, a rapidly developing field that promises to streamline genomic information and improve its diagnostic power.
Read more: Evolutionary information improves discovery of mutations associated with diseases
Melbourne researchers are now simulating in 3D, the motion of the complete human rhinovirus, the most frequent cause of the common cold, on Australia’s fastest supercomputer, paving the way for new drug development.
Source: The University of Melbourne
Roke Manor Research Ltd (Roke), a Chemring Group company, has developed the world’s first threat monitoring system for autonomous vehicles that emulates a mammal’s conditioned fear-response mechanism.
The STARTLE system uses a combination of artificial neural network and diagnostic expert systems to continually monitor and assess potential threats.
“Startle delivers local autonomy to a vehicle by providing a mechanism for machine situation awareness to efficiently detect and assess potential threats. This allows vehicle sensing and processing resources to be devoted to the assigned task, but if a threat is detected it will cue the other systems to deal with it swiftly before continuing its mission. These vital seconds could be the difference between mission failure and success.”
Source: Neuroscience News
'Stoned' gene key to maintaining normal brain function
July 6, 2012
(Medical Xpress) — Scientists at the University of Liverpool have found that a protein produced by a gene identified in fruitflies, is responsible for communication between nerve cells in the brain.
Dr Stephen Royle: “This research is another step towards fully understanding the complexities of the human brain.”
The ‘stoned’ gene was discovered in fruitflies by scientists in the 1970s. When this gene was mutated, the flies had problems walking and flying, giving rise to the term ‘stoned’ gene. The same gene was found in mammals some years later, but until now scientists have not known precisely what this gene is responsible for and why it causes problems with physical functions when it mutates.
‘Packets of chemicals’
Scientists at Liverpool have found that the protein the gene expresses in mammals, called stonin2, is responsible for retrieving ‘packets’ of chemicals that nerve cells in the brain release in order to communicate with each other. The inability of the gene to express this protein in the fruitfly study, suggests why the insect appeared not to be able to walk or fly normally.
The team used advanced techniques to inactivate stonin2 for short and long periods of time in animal cells grown in the laboratory. The cells used where from an area of the brain associated with learning and memory. They showed that without stonin2 the nerve cells could not retrieve the ‘packets’ needed to transport the chemicals required for communications between nerve cells.
Dr Stephen Royle, from the University’s Institute of Translational Medicine, explains: “Nerve cells in the brain communicate by releasing ‘packets’ of chemicals. These ‘packets’ must be retrieved and refilled with chemicals so that they can be used once again. This recycling programme is very important for nerve cells to keep communicating with each other.
“We have shown that a protein called stonin 2 is needed for the packets to be retrieved. There is currently no evidence to suggest that the gene which expresses this protein is mutated in human disease, but any failure in its function would be disastrous. The research is another step towards fully understanding the complexities of the human brain.”
The research is published in the journal, Current Biology.
Provided by University of Liverpool
Source: medicalxpress.com
Detector of DNA Damage: Structure of a Repair Factor Revealed
ScienceDaily (June 19, 2012) — Double-stranded breaks in cellular DNA can trigger tumorigenesis. LMU researchers have now determined the structure of a protein involved in the repair and signaling of DNA double-strand breaks. The work throws new light on the origins of neurodegenerative diseases and certain tumor types.
Agents such as radiation or environmental toxins can cause double-stranded breaks in genomic DNA, which facilitate the development of tumors or the neurodegenerative disorders ataxia telangiectasia (AT) and AT-like disease (ATLD). Hence efficient repair mechanisms are essential for cell survival and function. The so-called MRN complex is an important component of one such system, and its structure has just been elucidated by a team led by Professor Karl-Peter Hopfner of LMU’s Gene Center.
Malignant mutations
The MRN complex consists of the nuclease Mre11, the ATPase Rad50 and the protein Nbs1. Nbs1 is responsible for recruiting the protein ATM, which plays a central role in early stages of the cellular response to DNA damage, to the site of damage. “How the MRN complex actually recognizes double-stranded breaks is still not clear,” says Hopfner. He and his colleagues therefore set out to clarify the issue by analyzing the structures of mutant, functionally defective versions of the complex.
"We found that pairs of Mre11 molecules form a flexible dimer, which is stabilized by Nbs1." Mutations in different subunits of the complex are associated with distinct syndromes, marked by a predisposition to certain cancers, sensitivity to radiation or neurodegeneration. Hopfner’s results help to explain these differences. For instance, the mutation linked to ATLD lies within the zone of contact between Mre11 and Nbs1, and may inhibit activation of ATM by weakening their interaction.
Source: Science Daily
Noninvasive Genetic Test for Down Syndrome and Edwards Syndrome Highly Accurate
ScienceDaily (June 5, 2012) — Using a noninvasive test on maternal blood that deploys a novel biochemical assay and a new algorithm for analysis, scientists can detect, with a high degree of accuracy, the risk that a fetus has the chromosomal abnormalities that cause Down syndrome and a genetic disorder known as Edwards syndrome. The new approach is more scalable than other recently developed genetic screening tests and has the potential to reduce unnecessary amniocentesis or CVS.
Two studies evaluating this approach are available online in advance of publication in the April issue of the American Journal of Obstetrics & Gynecology (AJOG).
Diagnosis of fetal chromosomal abnormalities, or aneuploidies, relies on invasive testing by chorionic villous sampling or amniocentesis in pregnancies identified as high-risk. Although accurate, the tests are expensive and carry a risk of miscarriage. A technique known as massively parallel shotgun sequencing (MPSS) that analyzes cell-free DNA (cfDNA) from the mother’s plasma for fetal conditions has been used to detect trisomy 21 (T21) pregnancies, those with an extra copy of chromosome 21 that leads to Down syndrome, and trisomy 18 (T18), the chromosomal defect underlying Edwards syndrome. MPSS accurately identifies the conditions by analyzing the entire genome, but it requires a large amount of DNA sequencing, limiting its clinical usefulness.
Scientists at Aria Diagnostics in San Jose, CA developed a novel assay, Digital Analysis of Selected Regions (DANSR™), which sequences loci from only the chromosomes under investigation. The assay requires 10 times less DNA sequencing than MPSS approaches.
In the current study, the researchers report on a novel statistical algorithm, the Fetal-fraction Optimized Risk of Trisomy Evaluation (FORTE™), which considers age-related risks and the percentage of fetal DNA in the sample to provide an individualized risk score for trisomy. Explains author Ken Song, MD, “The higher the fraction of fetal cfDNA, the greater the difference in the number of cfDNA fragments originating from trisomic versus disomic [normal] chromosomes and hence the easier it is to detect trisomy. The FORTE algorithm explicitly accounts for fetal fraction in calculating trisomy risk.”
To test the performance of the DANSR/FORTE assay, Dr. Song and his colleagues evaluated a set of subjects consisting of 123 normal, 36 T21, and 8 T18 pregnancies. All samples were assigned FORTE odd scores for chromosome 18 and chromosome 21. The combination of DANSR and FORTE correctly identified all 36 cases of T21 and 8 cases of T18 as having a greater than 99% risk for each trisomy in a blinded analysis. There was at least a 1,000 fold magnitude separation in the risk score between trisomic and disomic samples.
In a related study, researchers from the Harris Birthright Research Centre for Fetal Medicine, Kings College Hospital, University of London and the University College London Hospital, University College London, provided 400 maternal plasma samples to Aria for analysis using the DANSR assay with the FORTE algorithm. The subjects were all at risk for aneuploidies, and they had been tested by chorionic villous sampling. The analysis distinguished all cases of T21 and 98% of T18 cases from euploid pregnancies. In all cases of T21, the estimated risk for this aneuploidy was greater than or equal to 99%, whereas in all normal pregnancies and those with T18, the risk score for T21 was less than or equal to 0.01%.
"Combining the DANSR assay with the FORTE algorithm provides a robust and accurate assessment of fetal trisomy risk," says Dr. Song. "Because DANSR allows analysis of specific genomic regions, it could be potentially used to evaluate genetic conditions other than trisomy. The incorporation of additional risk information, such as from ultrasonography, into the FORTE algorithm warrants investigation."
Kypros H. Nicolaides, MD, senior author of the University of London study, suggests that fetal trisomy evaluation with cfDNA testing will inevitably be introduced into clinical practice. “It would be useful as a secondary test contingent upon the results of a more universally applicable primary method of screening. The extent to which it could be applied as a universal screening tool depends on whether the cost becomes comparable to that of current methods of sonographic and biochemical testing.”
Dr. Nicolaides also notes that the plasma samples were obtained from high-risk pregnancies where there is some evidence of impaired placental function. It would also be necessary to demonstrate that the observed accuracy with cfDNA testing obtained from the investigation of pregnancies at high-risk for aneuploidies is applicable to the general population where the prevalence of fetal trisomy 21 is much lower. “This may well prove to be the case because the ability to detect aneuploidy with cfDNA is dependent upon assay precision and fetal DNA percentage in the sample rather than the prevalence of the disease in the study population,” he concludes.
Source: Science Daily
Teaching Tree-Thinking Through Touch
ScienceDaily (June 4, 2012) — A pair of new studies by computer scientists, biologists, and cognitive psychologists at Harvard, Northwestern, Wellesley, and Tufts suggest that collaborative touch-screen games have value beyond just play.
Multi-touch tables can recognize and accommodate several users at once, allowing students to collaborate and learn while they play an engaging game. (Credit: Michael Horn, Northwestern University)
Two games, developed with the goal of teaching important evolutionary concepts, were tested on families in a busy museum environment and on pairs of college students. In both cases, the educational games succeeded at making the process of learning difficult material engaging and collaborative.
The findings were presented at the Association for Computing Machinery (ACM) Special Interest Group on Computer-Human Interaction (SIGCHI) conference in May.
The games take advantage of the multi-touch-screen tabletop, which is essentially a desk-sized tablet computer. In a classroom or a museum, several users can gather around the table and use it simultaneously, either working on independent problems in the same space, or collaborating on a single project. The table accommodates multiple users and can also interact with physical objects like cards or blocks that are placed onto its surface.
The new research moves beyond the novelty of the system, however, and investigates the actual learning outcomes of educational games in both formal and informal settings.
"Do we know what the users are actually learning from this? That question is a step beyond the research of the past 10 years, where we’ve been seeing research publications that assess how well the system is performing, but not addressing how well it’s accomplishing what it’s really designed for," says principal investigator Chia Shen, a Senior Research Fellow in Computer Science at the Harvard School of Engineering and Applied Sciences (SEAS) and Director of the Scientists’ Discovery Room Lab.
The two collaborative games that have been developed for the system, Phylo-Genie and Build-a-Tree, are designed to help people understand phylogeny — specifically, the tree diagrams that evolutionary biologists use to indicate the evolutionary history of related species. Learners new to the discipline sometimes think of evolution as a linear progression, from the simple to the complex, with humans as the end point.
"What people are used to typically is geospatial data, like a map," explains Shen. "In phylogeny, however, the students need to understand that the relationship between species really depends on when they diverged. That’s represented by the position of the internal nodes of the tree, not by counting across the top of the tree, which is how many people intuitively do it."
The Phylo-Genie game, developed by researchers at Harvard, Wellesley, and Tufts, attempts to address the misconceptions that students hold even at the college level. Designed for a formal classroom setting, the game walks students through a scenario in which they have been bitten by an unusual species of snake and must identify its closest relatives in order to choose the correct anti-venom.
The researchers tested Phylo-Genie on pairs of undergraduate students who had not yet taken a course in evolutionary biology. Other pairs of students were given the same exercise, but in a pen-and-paper format. In comparison to the paper version, the electronic game produced statistically significantly higher scores on a post-test (an exam borrowed from a Harvard course), as well as higher participant ratings for engagement and collaboration.
Both of the phylogeny games were designed and evaluated in accordance with accepted principles of cognitive psychology and learning sciences.
The Build-a-Tree game was designed with an informal museum environment in mind. Researchers on this project, directed by lead author Michael S. Horn at Northwestern University and Shen at Harvard, observed 80 families and other social groups interacting with the Build-a-Tree game at the Harvard Museum of Natural History.
The game asks users to construct phylogenetic trees by dragging icons — for example, a bat, a bird, and a butterfly — toward one another in the correct order. As the user progresses through several levels, the problems become more challenging.
The idea, Shen says, is to encourage what museum science educators call “active prolonged engagement,” as opposed to “planned discovery.” The former allows learners to explore information independently and to interact with it in an open-ended manner; the latter approach, common in natural history museums, guides the user toward a particular set of facts.
"Natural history museums have always been a place where the exhibits are behind glass in the gallery," explains Shen. "You come here to see things that you just don’t see anywhere else — fossils millions of years old — and you come here to learn. You see school groups and parents coming in with a serious mind, and we’re breaking into that culture."
The Build-a-Tree game performed well against established measures of active prolonged engagement and social learning.
Even in the most high-tech exhibit hall, where visitors are engaged at every turn, it takes a great deal of creative thinking to demonstrate a phenomenon that is essentially imperceptible in real time.
"Evolution is a process that takes millions of years, whereas in chemistry or physics there are all sorts of phenomena that you can experiment with, like the tornado exhibit where you can go in and interrupt the air," says Shen. "This is our experiment: can we build something that is not as phenomenon-driven but can still engage them? I think we’ve succeeded in that."
Source: Science Daily