Keynote address at Georgetown University School of Nursing and Health Srudies 12th Annual Undersgraduate Research Conference and Introductory lecture to Georgetown University’s MOOC Course : Genomic Medicine Gets Personal
Category Archives: Biology & Life Sciences
Scientists Create an Unprecedented Map of the Developing Human Brain
at Wired By Greg Miller 04.02.14
The red and green brain slice (left) illustrates activity levels for a single gene. The multicolor slice (right) is a reference atlas, with different colors corresponding to different anatomical zones. Image: Miller et al., Nature
Scientists released the most detailed map ever made of the fetal human brain today. It contains a massive amount of information about gene activity at a crucial time in development — just as the cerebral cortex is developing. The scientists believe it holds important clues about the biological origins of disorders like autism, as well as insights into what makes the human brain unique.
Halfway through gestation, a human brain could fit in the palm of your hand. But it’s around this time that the cortex, which is responsible for many of our cognitive capabilities, is starting to take shape, says neuroscientist Ed Lein of the Allen Institute for Brain Science in Seattle, who led the new study.
To build the new atlas, Lein and colleagues constructed the map from four fetal brains obtained through a tissue bank. They sliced each one into about 3,000 ultra-thin sections. They used dyes and genetic markers on some of those slices to create a reference atlas. On other slices, they used microscopes equipped with laser beams to snip out tiny bits of tissue for genetic tests. The team looked at the activity level of about 20,000 genes, and they report their findings today in Nature.
There’s no doubt the fast pace of technology is making these massive datasets easier and faster to compile. But the promise of meaningful advances in understanding the brain and disorders of the brain won’t be delivered overnight. Even in this new era of Big Neuroscience, that’s still the hardest part.
The researchers have only begun to delve into this deep dataset, but Lein says they’ve already found some interesting things. For example, 34 genes whose sequences differ in interesting ways between humans and other primates appeared to be especially active in the developing frontal cortex. This is a region that’s relatively large in humans and thought to be especially important for social behavior, planning for the future, and other cognitive skills that humans excel at compared to many other species.
The team also investigated 78 genes identified in previous studies on autism and found that they appeared to be enriched in newly generated neurons in the cortex. “It tells you that the maturation of those neurons is where you want to look” for clues to the biology of autism, Lein said. (How that might fit with the recent finding of abnormal patches of cortex in the brains of autistic children — reported by Lein and colleagues last week — isn’t yet clear).
The atlas is just the latest released by the Allen Institute, whose previous efforts include atlases of gene activity in the adult human brain, as well as the adult brain and developing mouse brain. In another paper today in Nature, they report a detailed map of neural connections in the mouse brain.
MTH1 The story – revolutionary anti-cancer approach
The Helleday Laboratory proudly presents a novel concept of treating cancer, based on a general non-oncogene addition in cancer cells. The new concept is that cancer cells are killed by their own high level of intrinsic oxidative stress, not present in normal cells. We target the MTH1 protein required to prevent oxidative stress in cancer to become DNA damage. Normal cells have low level of oxidative stress and don’t need the MTH1 protein. See how the concept works!
Learn more about MTH1 and our revolutionary anti-cancer approach here: http://www.helleday.org
Stem cell ‘breakthrough data inappropriately handled’
Dr Haruko Obokata presented the breakthrough findings in January
An investigation into a supposedly groundbreaking stem cell study in Japan has discovered “inappropriate handling” of the data.
It was reported in January that dipping cells in acid could cheaply and quickly convert them into stem cells.
Questions were raised about the images used in the scientific report and other research groups have failed to reproduce the results.
The interim report has not found any evidence of research misconduct.
Stem cells can become any other type of tissue and are already being investigated to heal the damage caused by a heart attack and to restore sight to the blind.
The original study, published in the journal Nature, became a huge story globally and was described as “remarkable” and a “major scientific discovery”.
It offered a cheap and ethical source of stem cells that could have helped make them a practical treatment rather than a researcher’s dream.
Similar images
But significant doubts have emerged.
One centres on the use of images in the scientific report by the team at the Riken Centre for Developmental Biology.
They were similar to images from previous research by one of the scientists involved, Dr Haruko Obokata, which did not use the acid-bath technique.
Meanwhile, teams around the world have failed to produce stem cells using the reported technique.
A review by Prof Kenneth Ka-Ho Lee, at the Chinese University of Hong Kong, published on ResearchGate, concluded: “The ease and simplicity of their method for generating STAP cells [the name given to stem cells produced by this method] from various stressors and cell types have left the readers in doubt.
“We have tried our very best to generate STAP cells using their protocol and it appears that it is not as simple and reproducible as we expected.
“So whether the techniques really works still remains an open question.”
‘No malice’ intended
Riken launched an investigation and the first findings are now being reported.
It has found that some images had been “inadvertently” left in the report and there was “no malice” intended.
However, a conclusion has not yet been reached on allegations that part of the methodology had been copied from another scientific paper or that images in the paper resemble those from Dr Obokata’s previous research.
In a statement, the president of Riken, Prof Ryoji Noyori, said: “I would like, first and foremost, to express my deepest regrets that articles published in Nature by Riken scientists are bringing into question the credibility of the scientific community.
“It is extremely regrettable that significant discrepancies have been found to have been generated in the process of preparing the Nature articles for publication.
“We are investigating these discrepancies, with the understanding that it may become necessary to demand the withdrawal of the articles.”
This week, a member of the research group called for the findings to be withdrawn as it was no longer clear what was right.
Prof Teruhiko Wakayama, of the University of Yamanashi, told Japanese TV: “When conducting the experiment, I believed it was absolutely right.
“But now that many mistakes have emerged, I think it is best to withdraw the research paper once and, using correct data and correct pictures, to prove once again the paper is right.
“If it turns out to be wrong, we would need to make it clear why a thing like this happened.”
Unraveling a mystery in the ‘histone code’ shows how gene activity is inherited
Every cell in our body has exactly the same DNA, yet every cell is different. A cell’s identity is determined by the subset of genes that it activates. But how does a cell know which genes to turn off and which to turn on? While the genetic code carried in our DNA provides instructions for cells to manufacture specific proteins, it is a second code that determines which genes are in fact activated in particular cell types.
This second code is carried by proteins that attach to DNA. The code-carrying proteins are called histones. Today, researchers at Cold Spring Harbor Laboratory (CSHL) and colleagues publish research revealing a new layer of complexity in the histone code. They have found that the slightest variation in a single histone protein can have dramatic effects on how the genes encoded in our DNA are used.
Scientists have discovered a new mechanism that protects active genes from being silenced during cell division. They found that two variants of the same protein can distinguish active and inactive areas of the genome. The two variants differ by just one amino acid, circled here. Researchers captured the atomic structure of the two variants using a kind of molecular photography, shown here. They discovered that the single amino acid change is recognized by an enzyme (in red and blue here) that adds a silencing mark to only one variant (indicated with an arrow), instructing the cell to keep those areas of the genome inactive.
Histones are vitally important because our genetic material is vast: every cell in the body has more than six feet of DNA bundled within a tiny nucleus, a space much smaller than can be seen with the naked eye. For such a massive amount of DNA to be compacted into a microscopic space, it must be wound tightly around spool-like assemblies of proteins. Each of those spools is made up of eight histone proteins. It takes millions of spools in every cell to bundle the entire genome.
Histone proteins are marked with chemical tags, such as methyl groups. The histone code consists of the patterns formed by such marks, across the full genome. The marks are sometimes called epigenetic marks. “Epi” means, literally, “above” the genome. The “second” code consisting of these marks provides instructions that cause cells to turn specific genes on or off.
A tailor-made molecule against malaria
The malaria parasite is particularly pernicious since it is built to develop resistance to treatments. The lack of new therapeutic approaches also contributes to the persistence of this global scourge. A study led by Didier Picard, professor at the Faculty of Sciences of the University of Geneva (UNIGE), Switzerland, describes a new class of molecules targeting the two problems at the same time. Using ultra sophisticated computerised modelling tools, the researchers were successful in identifying a type of candidate molecules toxic for the pathogen, but not for the infected human red blood cells. The study, led in collaboration with researchers from the Geneva-Lausanne School of Pharmacy (EPGL) and the University of Basel, has been published in the Journal of Medicinal Chemistry.
The most severe form of malaria is caused by infection with Plasmodium falciparum. The eradication of this parasite is even more difficult as it becomes resistant to treatments. The group led by Didier Picard, professor of biology at the Faculty of Sciences of UNIGE, Switzerland, is closely interested in the protein Heat Shock Protein 90 (HSP90), which plays a central role for several factors involved in the life cycle, survival and resistance of the pathogen.
This is a modeled representation of an inhibitory molecule (yellow) in a “pocket ” of the HSP90 protein of the parasite (pink)
Expressed in organisms as diverse as bacteria and mammal cells, HSP90 acts as a “chaperone”, by helping other proteins during both normal and stressful periods. In the Plasmodium, HSP90 protects parasitic proteins during high fevers triggered by its presence. The chaperone also participates in the maturation of the pathogen in human red blood cells. “Our goal was to determine if there was a difference between the human form and the parasitic form of HSP90 that we could exploit for therapeutic purposes”, explains Tai Wang, a PhD student at the Department of Cell Biology of UNIGE.
The PhD student used ultra-sophisticated computerised modelling tools to characterise the various tridimensional conformations of the parasite’s HSP90. “The human chaperone harbours a “pocket” that binds molecules known to inhibit its activity. I compared it with that of the Plasmodium, hoping to find a difference which could be targeted by a specific inhibitor, but didn’t,” reported the researcher.
A screening performed entirely in silico
By studying the HSP90 of the pathogen from every possible angle, Tai Wang discovered another pocket capable of binding inhibitory substances, completely absent in its human alter ego. Using a supercomputer, he performed the screening of a virtual library containing more than a million chemical compounds while retaining those that could fit in this pocket. This screening in silico led him to select five candidates.
These experiments were then completed by a “real time” modelling technique. “The simulations were conducted to analyse the dynamics of interaction between the HSP90 and the candidates, leading to the discovery of inhibitors which interact specifically with the Plasmodium falciparum chaperone”.
The molecules were then tested in vitro in different systems. The biologists demonstrated in particular the toxicity of those inhibitors on Plasmodium falciparum cultures, in doses sufficient to kill the parasites without affecting the infected red blood cells.
“These recently patented molecules are part of a group of compounds related to the 7-azaindoles, which exclusively bind the HSP90 of the parasite, but not the human form. The next step will be to fine-tune them in order to perform clinical tests,” concluded Didier Picard.
New Sequencing Technologies
Biomedical Research Foundation of the Academy of Athens (BRFAA)
BRFAA at a Glance
The Biomedical Research Foundation of the Academy of Athens (BRFAA) is a non-profit institute dedicated to understanding, treating, and preventing human ailments through biomedical research. BRFAA seeks to serve science and medicine, and to participate fully in global innovation through its commitment to the true integration of biology, medicine, and informatics.
All faculty members have a track record of academic excellence and joined BRFAA from leading US and European Research and Clinical Centers. Their different expertise complement each other beautifully and result in a powerful scientific team. More than 300 postdoctoral fellows, laboratory technicians, and Ph.D. students work closely with the faculty to unravel the mechanisms behind fundamental human diseases such as diabetes, cancer, Alzheimer’s, cardiomyopathies etc. The Foundation is also fortunate to have a talented and dedicated administrative staff that supports the research and helps make this complex organization work smoothly and effectively. Everyone at BRFAA is committed to scientific excellence and integrity in all that they do and are dedicated to making a positive impact on improving human quality of life.
Established by the Academy of Athens, the Foundation accommodates state-of-the-art facilities over a 25.000 square meter area for conducting internationally competitive biomedical research. It is equipped with a rich variety of highly specialized scientific equipment. The rigorous research performed at BRFAA has received international recognition and has attracted generous funds from competitive research grants. Yet the most promising endeavor of the Foundation is establishing an institute of academic excellence where basic research and clinical application can come together to better serve human life.
Research Centers
Redesign My Brain Season 1 Full Episode 1 – Make Me Smarter
MAKE ME SMARTER features Dr Michael Merzenich, the pioneer of the neuroplasticity revolution, as he teaches Todd how to turbo charge his Thinking Speed, Attention and Memory. After only a few weeks of brain training Todd attempts an extreme challenge at the World Memory Championships.
http://www.youtube.com/watch?v=Vv-1e1O056o
REDESIGN MY BRAIN features Australian personality Todd Sampson put brain training to the test as he undergoes a radical brain makeover to showcase the revolutionary new science of brain plasticity. In a TV first, we take viewers on an inspirational journey as Todd learns how science can turn an ordinary brain into a super brain in just three months. Today, anyone can become smarter, improve their memory and reverse mental ageing. So under the guidance of the world’s top scientists, Todd trains his brain to attain improved Cognition, enhanced Creativity and a stronger connection between Mind and Body.
ERC Consolidator Grants: Nearly €575 million to 312 mid-career top researchers
PN. Two (2) Greek Projects awarded
Press release, 14 January 2014
ERC Consolidator Grants: Nearly €575 million to 312 mid-career top researchers
The European Research Council (ERC) has today selected 312 top scientists in its first Consolidator Grant competition. These mid-career scientists are awarded a total of nearly €575 million. Grants are worth up to €2.75 million each, with an average of €1.84 million per grant. This new funding will enable already independent excellent researchers to consolidate their own research teams and to develop their most innovative ideas across the European Research Area.
The projects selected in this call cover a wide range of topics: using a geochemical clock to predict volcanic eruptions; exploring the effects of Dark Matter and Dark Energy on gravitational theory; checking responsibility, liability and risk in situations where tasks are delegated to intelligent systems; and investigating the role of genetic and environmental factors in embryo brain wiring. (For further information, click here)
On this occasion, European Commissioner for Research, Innovation and Science Máire Geoghegan-Quinn said: “These researchers are doing ground-breaking work that will advance our knowledge and make a difference to society. The ERC is supporting them at a key moment where funding is often hard to come by: when they need to move forward in their career and develop their own research and teams.”
The newly appointed President of the ERC, Professor Jean-Pierre Bourguignon commented: “The new year starts with the conclusion of the first competition for Consolidator Grants and I am very impressed by the quality of the selected projects. Judging by the ever increasing demand for ERC grants, especially from early- and mid-career researchers, it is clear that funding of this kind is much needed. Taking a broader view, I am pleased to have embarked on a new challenge as head of this organisation, which has achieved world-class status in a very short time. It’s pivotal for Europe to create conditions for its new generation of researchers to thrive while following their scientific curiosity.”
With over 3600 proposals submitted, the demand for these grants rose by 46% this year, compared to the corresponding group of applicants in 2012. The ERC Consolidator Grant scheme targets researchers with seven to twelve years’ experience after their PhD, a period of the scientific career covered until 2012 under the Starting Grant scheme.
The share of women amongst the successful candidates in this call (24%) increased in comparison with the equivalent group of mid-career researchers in 2012 (22.5%). The average age of the selected researchers is 39. The overall success rate is 8.5%.
The ERC calls target top researchers of any nationality based in, or willing to move to,
Europe. In this call, grants are awarded to researchers of 33 different nationalities, hosted in
institutions located in 21 different countries throughout Europe, with nine of them hosting five
grantees or more. In terms of host institutions, the UK (62 grants), Germany (43) and France
(42) are in the lead. Researchers are also hosted in the Netherlands, Switzerland, Spain,
Italy, Israel, Belgium, Sweden, Austria, Denmark, Finland, Portugal, Greece, Hungary,
Ireland, Turkey, Cyprus, the Czech Republic and Norway. In terms of researchers’
nationality, Germans (48 grants) and Italians (46) are at the top, followed by French (33),
British (31) and Dutch (27) researchers. (See statistics here).
Around 45% of the grantees selected are in the domain ‘Physical Sciences and Engineering’,
37% in ‘Life Sciences’ and almost 19% in ‘Social Sciences and Humanities’. The grantees
were selected through peer review evaluation by 25 panels composed of renowned scientists
from around the world.
The grants in this latest competition will allow the scientists selected to engage in total an
estimated 1100 postdocs and PhD students as ERC team members. As a result the ERC
contributes to the development of a new generation of top researchers in Europe.
The 2014 ERC ‘Consolidator Grant’ call, the first one under Horizon 2020, is already open
and the deadline for all domains in this call is 20 May 2014.
Lists of selected researchers
The lists below show the proposals selected for funding.
LIST of all selected researchers by country of host institution (alphabetical order within
each country group)
Lists of selected researchers by domain (in alphabetical order):
Physical Sciences and Engineering
Life Sciences
Social Sciences and Humanities
STATISTICS – Consolidator Grants call (indicative)
DISCOVER MORE PROJECTS in this Consolidator Grants call
Background
Set up in 2007 by the EU, the European Research Council is the first pan-European funding organisation for frontier research. It aims to stimulate scientific excellence in Europe by encouraging competition for funding between the very best, creative researchers of any nationality and age. The ERC also strives to attract top researchers from anywhere in the world to come to Europe. It funds young, early-career top researchers (‘ERC Starting Grants’), already independent excellent scientists (‘ERC Consolidator Grants’), and senior research leaders (‘ERC Advanced Grants’). The substantial funding can amount to a maximum of €2 million for a Starting Grant, €2.75 million for a Consolidator Grant and €3.5 million for an Advanced Grant.
The ERC operates according to an “investigator-driven” (or “bottom-up”) approach, allowing researchers to identify new opportunities in any field of research, without thematic priorities. From 2007 to 2013 under the seventh EU Research Framework Programme (FP7), the ERC’s budget was €7.5 billion. Under the new Framework Programme for Research and Innovation (2014-2020), Horizon 2020, the ERC has a substantially increased budget of over €13 billion.
Since its launch, the ERC has funded some 4000 researchers and their frontier research projects and has become a “benchmark” for the competitiveness of national research systems, complementing existing funding schemes at national and European levels.
The ERC is led by the ERC Scientific Council, composed of 22 top scientists and scholars, including the ERC President Professor Jean-Pierre Bourguignon, who took office on 1 January 2014. The ERC Executive Agency implements the ERC component of the Horizon 2020 Programme and is led by Director Pablo Amor.
Due to increasing submission numbers, since 2013 the ERC Starting Grant scheme has been split in two: the ERC Starting Grant, for researchers with at least 2 and up to 7 years’ experience after their PhD; and the new ERC Consolidator Grant for researchers with over 7 and up to 12 years’ experience after their PhD. The 2012 Starting Grant call had two sub-streams (“starters” and “consolidators”), which corresponded to the current division. Any comparative analyses made in this press release are based on the equivalent categories in previous calls (7–12 years post-PhD experience).
The ERC Consolidator Grant in brief
For top researchers of any nationality and age, with over 7 and up to 12 years of experience after PhD, and a scientific track record showing great promise.
Based on a simple approach: 1 researcher, 1 host institution, 1 project, 1 selection criterion: excellence.
Host institution should be based in the European Research Area (EU Member States plus countries associated with the EU research programme). No consortia. No co-funding is required.
Funding: up to €2.75 million per grant for up to 5 years.
Calls for proposals: published annually. See updated information on the upcoming calls here.