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Complex Insight  - Understanding our world
News and notes on complex systems in life sciences, engineering, education and government
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Scientists demonstrate path to linking the genome to healthy tissues and disease

Scientists demonstrate path to linking the genome to healthy tissues and disease | Complex Insight  - Understanding our world | Scoop.it

A study by an international consortium of scientists reached a major milestone in establishing a baseline understanding of gene expression across healthy human tissues, and linking genes to disease.


Via Integrated DNA Technologies
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Genetics may lie at the heart of crop yield limitation - EurekAlert (2017) 

Genetics may lie at the heart of crop yield limitation - EurekAlert (2017)  | Complex Insight  - Understanding our world | Scoop.it

You might think that plants grow according to how much nutrition, water and sunlight they are exposed to, but new research... shows that the plant's own genetics may be the real limiting factor.

"This could have potentially big implications for the agricultural industry... Our model plant is in the same family as cabbages, so it's easy to imagine creating giant cabbages or growing them to the desired market size faster than at present."

It was previously assumed that plant growth was generally resource-limited, meaning that plants would only grow as large and fast as they could photosynthesise. However, Dr Pullen and his team present evidence that plant growth is actually "sink-limited", meaning that genetic regulation and cell division rates have a much bigger role in controlling plant growth than previously thought: 


"We are proposing that plant growth is not physically limited by Net Primary Productivity (NPP) or the environment, but instead is limited genetically in response to these signals to ensure they do not become limiting."

By genetically altering the growth repressors in Arabidopsis, Dr Pullen and his team were able to create mutant strains. They identified the metabolic rates of the different plant strains... as well as comparing the size and weight of the plants... also grew the mutant plant strains at different temperatures to see if this changed their results: "When grown at different temperatures we still find a difference in size"...  

The impact of these results is wide-reaching, and... it may even change how we think about global climate data: "Climate models need to incorporate genetic elements because at present most do not, and their predictions would be much improved with a better understanding of plant carbon demand." 


https://www.eurekalert.org/pub_releases/2017-07/sfeb-gml070117.php



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CRISPR-Cas Genome Surgery in Ophthalmology

Genetic disease affecting vision can significantly impact patient quality of life. Gene therapy seeks to slow the progression of these diseases by treating the underlying etiology at the level of the genome. Clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated systems (Cas) represent powerful tools for studying diseases through the creation of model organisms generated by targeted modification and by the correction of disease mutations for therapeutic purposes. CRISPR-Cas systems have been applied successfully to the visual sciences and study of ophthalmic disease - from the modification of zebrafish and mammalian models of eye development and disease, to the correction of pathogenic mutations in patient-derived stem cells. Recent advances in CRISPR-Cas delivery and optimization boast improved functionality that continues to enhance genome-engineering applications in the eye. This review provides a synopsis of the recent implementations of CRISPR-Cas tools in the field of ophthalmology.

Via Gerd Moe-Behrens
Phillip Trotter's insight:
While the promise of CRISPR was not that it would change how genetics and biology behaved its quickly becoming hyped that way in popular press.  The fact that the Cas9 protein can be used as a cheap and fast technique to co-localize with specific DNA sequences is undoubtedly incredibly useful. As researchers discover mechanisms where they can exploit co-localization and modification at specific sites using DNA cleavage capabilities it is important we get well informed reviews of actual applications as well as coverage of potential ones.  This paper gives a good summary of recent developments and insights to applications of CRISPR-CAS in ophthalmology  for both better understanding visual systems and potential treatments for ophthalmic disease. 
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Chemicals That Make Plants Defend Themselves Could Replace Pesticides - Elsevier (2015)

Chemical triggers that make plants defend themselves against insects could replace pesticides, causing less damage to the environment. New research... identifies five chemicals that trigger rice plants to fend off a common pest – the white-backed planthopper, Sogatella furcifera

 

Pesticides are used around the world to control insects that destroy crops... One of the problems with many pesticides is that they kill indiscriminately. For rice plants, this means pesticides kill the natural enemies of one of their biggest pests, the white-backed planthopper... This pest... causes the plants to wilt and can damage the grains. It also transmits a virus disease... which stunts the plants’ growth and stops them from “heading,” which is when pollination occurs.

 

Left untreated, many of the insects’ eggs would be eaten, but when pesticides are used these hatch, leading to even more insects on the plants. What’s more, in some areas as many as a third of the planthoppers are resistant to pesticides... “Therefore, developing safe and effective methods to control insect pests is highly desired”... 

 

Because of the problems of using pesticides, it’s vital to find new solutions to help protect rice plants from infestation. Plants have natural self-defense mechanisms that kick in when they are infested with pests like the planthopper. This defense mechanism can be switched on using chemicals that do not harm the environment and are not toxic to the insects or their natural enemies... 

 

Researchers... developed a new way of identifying these chemicals. Using a specially designed screening system, they determined to what extent different chemicals switched on the plants’ defense mechanism... The researchers used bioassays to show that these chemicals could trigger the plant defense mechanism and repel the white-backed planthopper. This suggests that these chemicals have the potential to be used in insect pest management... 

 

“This new approach to pest management could help protect the ecosystem while defending important crops against attack.”

The next step for the research will be to explore how effective the chemicals are at boosting the plants’ defenses and controlling planthoppers in the field.

 

https://www.elsevier.com/about/press-releases/research-and-journals/chemicals-that-make-plants-defend-themselves-could-replace-pesticides

 

Original article: http://dx.doi.org/10.1016/j.bmcl.2015.10.041

 


Via Alexander J. Stein
Phillip Trotter's insight:

Its good to see more research in these areas - but it would be good if in parallel we looked at potential impact of activated and elevated triggers and response  in terms of ecosystems and human health.  Multi-systemic approaches are going to be increasingly needed, which is worrying given how limited funding in this area already is..

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First CRISPR Gene Drive in Mosquitoes Aims to Eradicate Malaria

First CRISPR Gene Drive in Mosquitoes Aims to Eradicate Malaria | Complex Insight  - Understanding our world | Scoop.it
The students in Anthony James’s basement insectary at the University of California, Irvine, knew they’d broken the laws of evolution when they looked at the mosquitoes’ eyes.

By rights, the bugs, born from fathers with fluorescent red eyes and mothers with normal ones, should have come out only about half red. Instead, as they counted them, first a few and then by the hundreds, they found 99 percent had glowing eyes.

More important than the eye color is that James’s mosquitoes also carry genes that stop the malaria parasite from growing. If these insects were ever released in the wild, their “selfish” genetic cargo would spread inexorably through mosquito populations, and potentially stop the transmission of malaria.

The technology, called a “gene drive,” was built using the gene-editing technology known as CRISPR and is being reported by James, a specialist in mosquito biology, and a half dozen colleagues today in the Proceedings of the National Academy of Sciences.

A functioning gene drive in mosquitoes has been anticipated for more than a decade by public health organizations as a revolutionary novel way to fight malaria. Now that it’s a reality, however, the work raises questions over whether the technology is safe enough to ever be released into the wild.

“This is a major advance because it shows that gene drives will likely be effective in mosquitoes,” says Kevin Esvelt, a gene drive researcher at Harvard University’s Wyss Institute. “Technology is no longer the limitation.”

Starting last summer, Esvelt and other scientists began warning that gene drives were about to jump from theory to reality (see “Protect Society from Our Inventions, Says Genome Editing Scientists”) and needed more attention by regulators and the public. The National Academy of Sciences is studying the science and ethics of the technology and plans to release recommendations next year on “responsible conduct” by scientists and companies.

Gene drives are just the latest example of the fantastic power of CRISPR editing to alter the DNA of living things, which has already set off a debate over the possibility that gene editing could be used to generate designer human babies (see “Engineering the Perfect Baby”). But Henry Greely, a law professor and bioethics specialist at Stanford, says environmental uses are more worrisome than a few modified people. “The possibility of remaking the biosphere is enormously significant, and a lot closer to realization,” he says.

Malaria is caused when a mosquito bite transmits plasmodium, a single-celled parasite. It’s treatable, yet every year, 670,000 people die from malaria, the majority of them young children in sub-Saharan Africa.

James says his mosquitoes are the culmination of decades of mostly obscure, unheralded work by a few insect specialists toward constructing a genetic solution to malaria. It finally became possible this year when scientists in the laboratory of Ethan Bier, a fly biologist at the University of California, San Diego, who is a coauthor of the paper, finally used CRISPR to perfect a molecular “motor” that could allow the anti-malaria genes to spread.

The mosquitoes have two important genetic additions. One is genes that manufacture antibodies whenever a female mosquito has a “blood meal.” Those antibodies bind to the parasite’s surface and halt its development. Yet normally, such an engineered mosquito would pass the genes only to exactly half its offspring, since there’s a 50 percent chance any chunk of DNA would come from its mate. And since the new genes probably don’t help a mosquito much, they’d quickly peter out in the wild.

That’s where CRISPR comes in. In a gene drive, components of the CRISPR system are added such that any normal gene gets edited and the genetic cargo is added to it as well. In James’s lab, practically all the mosquitoes ended up with the genetic addition, a result Esvelt calls “astounding.”

What worries Esvelt is that, in his opinion, the California researchers haven’t used strict enough safety measures. He says locked doors and closed cages aren’t enough. He wants them to install a genetic “reversal drive” so the change can be undone, if necessary. “An accidental release would be a disaster with potentially devastating consequences for public trust in science and especially gene-drive interventions,” he says. “No gene-drive intervention must ever be released without popular support.”

James says the experiment was safe since the mosquitoes are kept behind a series of locked, card-entry doors and because they aren’t native to California. If any escaped, they wouldn’t be able to reproduce.

In fact, the whole point of a gene drive is to release it into the wild, a concept that has long been accepted, at least in theory, by public health organizations including the Gates Foundation. Now that they’re actually possible, however, alarming news headlines have compared the technology to “the next weapon of mass destruction” and even raised the specter of insect terrorism, such as mosquitoes that kill people with a toxin.

Gene-drive terrorism is probably nonsense, at least for now. That’s because even if insect weapons were possible, in practice it’s unlikely a terrorist organization would invest millions in an advanced genetic-engineering program. “I have been thinking quite a bit about bad things you could do with it, and we haven’t come up with anything that would succeed,” says Bier. “There are so many bad things you could do that are easier.”

Instead, Bier and James say they are convinced that engineered mosquitoes should be released as soon as possible, something they hope to do if they can find a community affected by malaria that will agree to it. “Imagine we could design a mosquito that would magically cure cancer,” says Bier. “Well, the fear of getting malaria is the same fear we have of getting cancer. In my opinion the benefits outweigh the risks, and we should move forward as aggressively as we can.”

Via Gerd Moe-Behrens
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The man who grew eyes

The man who grew eyes | Complex Insight  - Understanding our world | Scoop.it
Growing nerve tissue and organs is a sci-fi dream. Moheb Costandi met the pioneering researcher who grew eyes and brain cells.
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Interesting article on the work of Yoshiki Sasai  a Japanese biologist and Director of the Laboratory for Organogenesis and Neurogenesis at the research institute RIKEN in Kobe, Japan. Sasai was best known for developing new methods to grow stem cells into organ-like structures

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Researchers glimpse microbial 'dark matter'

Researchers glimpse microbial 'dark matter' | Complex Insight  - Understanding our world | Scoop.it

Led by Tanja Woyke, a microbiologist at the US Department of Energy’s Joint Genome Institute in Walnut Creek, California, researchers used single-cell sequencing to read the genomes of 201 bacterial and archaeal cells taken from nine diverse environments, such as hydrothermal vents and an underground gold mine. None of the organisms had ever been sequenced or cultivated in a laboratory. The results are published today in Nature1.

Phillip Trotter's insight:

The ability to use single cell sequencing gives a whole new insight into microbial and bacterial worlds. The research highlights not only how we will be reassessing our definitions and classifications of bacterial and archaeal kingdoms but also the range of adaptations that wait to be discovered.

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Gene therapy trial 'cures children'

Gene therapy trial 'cures children' | Complex Insight  - Understanding our world | Scoop.it
A disease which robs children of the ability to walk and talk has been cured by pioneering gene therapy to correct errors in their DNA, say doctors.
Phillip Trotter's insight:

After the initial hype around gene therapy, fast solutions failed to meet expectations.  Following a death in one trial and other patients developed leukaemia  studies showed that  introducing new and modified genes could activate cancer genes. Since then safety concerns have been high. The first gene therapy trials in europe were not approved until 2012.  The BBC article describes a new technique developed at the San Raffaele Scientific Institute in Milan, Italy  for children born with metachromatic leukodystrophy.  Babies born with metachromatic leukodystrophy appear healthy, but their development starts to reverse between the ages of one and two as part of their brain is destroyed. Three children  with the disease underwent the treatment and have so far showed normal development with  no side effects. While the patients will continue to be followed, the treatment shows that some of the potential promises of gene therapy may come true. 

 

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Honey bees' genetic code unlocked

Honey bees' genetic code unlocked | Complex Insight  - Understanding our world | Scoop.it

Researchers believe they have unlocked the genetic secrets as to why honey bees are so sensitive to environmental change. One of the reported findings suggests that development variation between worker bees and queens is the result of diet and a "histone code" - a process that sees genetic changes made to proteins called histones within cells' nuclei. Rather than "genetic" changes that are locked into DNA, these are known as "epigenetic" changes. The report marks the first time such effects had been recorded in honey bees. Click on image or title to learn more.

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Designing Drugs Aimed at a Different Part of Life’s Code

Designing Drugs Aimed at a Different Part of Life’s Code | Complex Insight  - Understanding our world | Scoop.it

Most drugs work by tinkering with the behavior of proteins. Like meddlesome coworkers, these molecules are designed to latch onto their target proteins and keep them from doing what they need to do.


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A decade of discovery: CRISPR functions and applications

A decade of discovery: CRISPR functions and applications | Complex Insight  - Understanding our world | Scoop.it
This year marks the tenth anniversary of the identification of the biological function of CRISPR–Cas as adaptive immune systems in bacteria. In just a decade, the characterization of CRISPR–Cas systems has established a novel means of adaptive immunity in bacteria and archaea and deepened our understanding of the interplay between prokaryotes and their environment, and CRISPR-based molecular machines have been repurposed to enable a genome editing revolution. Here, we look back on the historical milestones that have paved the way for the discovery of CRISPR and its function, and discuss the related technological applications that have emerged, with a focus on microbiology. Lastly, we provide a perspective on the impacts the field has had on science and beyond.

Via Gerd Moe-Behrens
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Great insight and perspective on CRISPR  developments and applications - worth reading.
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A Safety and Efficacy Study of TALEN and CRISPR/Cas9 in the Treatment of HPV-related Cervical Intraepithelial Neoplasia

This is an open-label and triple cohort study of the safety and efficacy of TALEN and CRISPR/Cas9 to possibly treat HPV Persistency and human cervical intraepithelial neoplasiaⅠwithout invasion.

Via Gerd Moe-Behrens
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If your tracking CRISPR/Cas9 applications - this is worth reviewing.
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Whatever happened to 'bans' on GM produce in British supermarkets? - Conversation (2015)

Whatever happened to 'bans' on GM produce in British supermarkets? - Conversation (2015) | Complex Insight  - Understanding our world | Scoop.it

In the late 1990s, Sainsbury’s and Safeway... both offered GM tomato purée... GM and non-GM cans of purée stood side by side on their shelves, the former some 18% cheaper... The cans were conspicuously labelled and pamphlets explaining what GM was all about were to hand nearby. But when the stock ran out and it was time to re-order, the anti-GM food balloon had gone up and the product was discontinued... 

In 1999 Marks & Spencer announced that it was removing all GM foods from its shelves. (In a House of Lords inquiry at that time, M&S said their customers demanded it. When asked by their lordships how many customers that meant, it turned out to have been rather a small percentage. But those who positively wanted GM were, it seems, even fewer in number)... 

All the other retailers followed suit: the UK’s retail industry was to be GM-free – or was it? In fact some GM products... were always to be found... Then there is the question of GM fodder for animals.... retailers said that they would not sell any products from pigs or poultry that had been exposed to GM feeds...


Until, that is, when Asda became the first of the leading UK supermarkets to abandon its commitment to eggs and poultry fed with GM in 2010... But by then public opinion on the issue had become almost completely mute... GM-feed for pigs and poultry was no longer to be excluded... there appears to have been no noticeable consumer rejection of products from animals fed GM...

More than half the world’s cotton is GM, so this is likely to be the case with products on sale in the UK. There is no obligation to label GM cotton so one cannot be sure, but nobody seems to ask and few seem to care... 


Public interest in this subject has largely waned... Though one can never be quite sure, it does begin to look as though the GM issue will fade away in the fullness of time, in England at least, even if it takes a while. I suspect GM food and crops will become commonplace and the protesting community will veer off in another direction, chasing new demons.

 

https://theconversation.com/whatever-happened-to-bans-on-gm-produce-in-british-supermarkets-51153

 


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Can CRISPR Avoid the Monsanto Problem?

Can CRISPR Avoid the Monsanto Problem? | Complex Insight  - Understanding our world | Scoop.it

It is distressing, but a fact, that the more rapidly any technology is adopted by scientists the more likely it is to leave people confused, anxious, and suspicious. This week, I wrote an article for the magazine about just such a revolutionary technique, called CRISPR, that permits scientists to edit the DNA of plants and animals with an ease and a precision that even a decade ago seemed inconceivable.

CRISPR research has already begun to transform molecular biology. There have been bold new claims about its promise and powers nearly every day. Yet, for the past fifty years, at least since Watson and Crick demonstrated that DNA contained the blueprints required to build everything alive, modern science has been caught in a hype trap. After all, if we possess such exquisitely detailed instructions, shouldn’t they be able to help us fix the broken genes that cause so many of our diseases?

The assumption has long been that the answer is yes. And for decades, we have been told (by the medical establishment, by pharmaceutical companies, and, sadly, by the press) that our knowledge of genetics will soon help us solve nearly every malady, whether it affects humans, other animals, or plants.

It turns out, however, that genetics and magic are two different things. Deciphering the blueprints in the three billion pairs of chemical letters which make up the human genome has been even more complex than anyone had imagined. And even though the advances have been real, and often dramatic, it doesn’t always seem that way. This has led many people to discount, and even fear, our most promising technologies. Somehow, we take lessons more readily from movies like “Jurassic Park” and “Gattaca” than from the very real, though largely incremental, advances in medical treatments.

This dangerous disconnect between scientific possibility and tangible results has already caused great harm: a scientifically unjustified fear of G.M.O.s, for example, has prevented many potentially life-enhancing crops from even being tested, let alone planted widely. The death of one patient, in 1999, halted all human-gene-therapy experiments in the United States for several years. We should, of course, be exceedingly cautious with such research, but if the U.S. is going to stop studies that could potentially help millions of people there are costs to that, too. (It’s worth remembering that there are real risks to everything we do: aspirin kills hundreds of Americans every year, and in the first half of 2015 nearly twenty thousand people have died in car accidents.)

Because it makes manipulating genes so much easier, CRISPR offers researchers the ability to rapidly accelerate studies of many types of illness, including cancers, autism, and AIDS. It will also make it possible to alter the genes of plants so that they can resist various diseases (without introducing the DNA of a foreign organism, which is how G.M.O.s are made). With CRISPR, almost anything could become possible: You want a unicorn? Just tweak the horse genome. How about a truly blue rose? The gene for the blue pigment does not exist naturally in roses. With CRISPR, it should be a trivial matter simply to edit that gene in.

Eventually, CRISPR should also permit technicians to edit embryos, which, at least in theory, could change the genetic lineage of mankind. The prospect is at least as frightening as it is exciting, and we need to start talking about that now. In the press, at least, that conversation—about perhaps the most exciting advance in the history of molecular biology—seems to have started. Two of the researchers I focussed on in my piece for The New Yorker have also been featured in other publications in the past two weeks: the Times has a profile of Jennifer Doudna, the Berkeley biochemist who helped figure out how to program CRISPR molecules to edit DNA, and STAT, a new online health and science publication launched by the Boston Globe’s owner, has one about Feng Zhang, a pioneering biologist at the Broad Institute of Harvard and M.I.T., who first made the technology work in mammals. The subject will soon get even more attention. Early next month, the National Academy of Sciences will convene an international conference devoted to the ethical use of this powerful new tool.


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Twins’ immune systems look like those of complete strangers

Twins’ immune systems look like those of complete strangers | Complex Insight  - Understanding our world | Scoop.it
When it comes to our immune response, genetics takes a back seat to pathogens.
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Our adaptive immune system, the one that responds to specific pathogens, relies on T cells and B cells. These cells make proteins that have a key job: distinguish between the harmless proteins in all of our cells and foreign proteins that may be harmful. In T cells, these molecules are creatively called T cell receptors (TCRs), and in B cells they are antibodies.

 
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Genomics: The single life

Genomics: The single life | Complex Insight  - Understanding our world | Scoop.it
Sequencing DNA from individual cells is changing the way that researchers think of humans as a whole.
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Human genomes such as cancer have been traditionally sequenced from DNA extracted from multiple cells. With certain cancers we know that local individual cellular adaptations, mutations and variation impact gene expression, cell behaviour and drug response.  Nicholas Navin pioneered a new approach for single cell sequencing pioneered  in order to sequence individual cancer cells and map local mutations and adaptations. Timour Basian and team inspired by Navin's work, helped perfect techniques for single cell sequencing while dramatically reduced sequencing pricing from $1000 per single cell to approx $60 per cell.  The article discuses further developments, implications and potential opportunities created by the advent of single cell sequencing. Worth reading.

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The Case of the Missing Human Ancestor

The Case of the Missing Human Ancestor | Complex Insight  - Understanding our world | Scoop.it
DNA from a cave in Russia adds a mysterious new member to the human family.
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Interesting article on the discovery of Denisovan DNA by the evolutionary genetics team at the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany. 

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Cancers Genomes and their Implications for Curing Cancer (by Bert Vogelstein, JHU)

The full lecture title is "Cancers - Their Genomes, Microenvironments, and Susceptibility to Bacteria-based Therapies" by Bert Vogelstein. The Johns Hopkins Center for Biotechnology Education and the Department of Biology in the Krieger School of Arts and Sciences hosted the American Society for Microbiology's Conference for Undergraduate Educators (ASMCUE) on the Homewood campus. Bert Vogelstein gave the closing plenary lecture, "Cancers - Their Genomes, Microenvironments, and Susceptibility to Bacteria-based Therapies". He teaches at John Hopkins University.

ASMCUE, now in its 18th year, is a professional development conference for approximately 300 educators. Each year, its steering committee organizes a program that offers access to premier scientists in diverse specialties and to educators leading biology education reform efforts. For more information on the conference, go to http://www.asmcue.org/page02d.shtml


Via Dr. Stefan Gruenwald
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