and died at Wuppertal Zoo
wow he died here
and died at Wuppertal Zoo
wow he died here
amicus curiae
an impartial advisor
Biodiversity
surprised to see australia in red, bc people dont inhabit most of the land
Serendipitous
the brooklyn museum website did a good job of this by giving a list of umbrella categories like "egyptian" and then you could fin artifacts you were not looking for initially
The Brooklyn Museum’s Collections Browse site
i like this website-- it is uniform, modern, navigable, and extremely informative
Visual appeal is critical for first impressions,
dont want a site that looks unreliable, old, or simply has too much going on (ads etc)
Though digitisation does not mean we can discard the physical specimens (they serve as the gold-standard of the digital information), it does mean the specimens can become more widely accessible.
if u cant make it to the actual place, you can acces them online
In these situations, perhaps virtual explorations of natural history are the most humane and democratic access points for exploring natural history.
bc it lowers environmental impacts
Digital platforms are often claimed to enhance engagement, through aesthetic and/or interactivity, but when compared to the real thing, do they?
lacks smell, touch, taste etc. beyond the obvious diff in sight
10 March 2016
How much has changed since this was published?
You need to always think about what biological problems need to be solved
As we know, biology is full of questions that have not yet been answered. I think this technology could help biologists answer many of these questions. That could lead to huge improvements in the field and even in the technology itself!
he aims to use gene editing to model neurodegenerative conditions such as Alzheimer's disease and Parkinson's disease in cell cultures and marmoset monkeys
This is another issue that is often raised in the debate over ethics. Is it ethical to experiment with this technology on living creatures such as these? Do the benefits outweigh the downfalls?
Introducing all of those mutations into a mouse the old-fashioned way would have been costly and time-consuming
Mutating mice "the old-fashioned way" often means breading generations of mice and trying to breed the perfect homozygous mouse. This is much more straight forward and effective.
effects are permanent
This is commonly cited in the dispute over ethics. If a mistake is made or something goes wrong, it is irreversible.
It lets them engineer more animals, in more complex ways, and in a wider range of species. Xue, who now runs his own lab at the University of Massachusetts Medical School in Worcester, is systematically sifting through data from tumour genomes, using CRISPR–Cas9 to model the mutations in cells grown in culture and in animals.
This shows the advantage over- for example- knock out mice. It takes much less time and can have very similar results with more consistency.
neurodegeneration
This is when neurons in the brain rapidly deteriorate.
a few weeks later
Highlights the enormous difference in required resources and accessibility of CRISPR-Cas9.
The cost: a year and US$20,000.
This is a perfect example of why many parts of the world could not previously use this technology. Because it simply required a lot of resources.
It's a first-generation tool
So, while CRIPSR needs to be improved in the field of accuracy, it also needs to be made more efficient?
doxycycline
Doxycycline is a broad-spectrum antibiotics of the tetracycline group. It lasts an unusually long time in the human body.
colorectal
This is cancer of the colon or rectum.
The resulting system triggers gene expression when cells are exposed to the light, and stops it when the light is flicked off
This strengthens the "stoplight" analogy, in which turning on and off or even pausing gene expression is like a traffic light.
transiently
This means something that is quickly passed over.
drug screening and cell therapies
One of many possible applications of the technology.
But Agami notes that few alternative enzymes found so far work as well as the most popular Cas9
What is it that makes the other tested enzymes less effective?
But for those who want to make very specific changes to short, non-coding RNAs, the options can be limited.
So, despite being very accurate and effective compared to other gene editing technology, CRISPR-Cas9 is still not perfect.
Delving into this dark matter
"dark matter": was that intentional, or is it just a common phrase?
used the technique to create mutations across a 40,000-letter sequence
That experiment likely took a long time, requiring precision and resources that are hard to come across.
More surprises may be in store as researchers harness CRISPR–Cas9 to probe large stretches of regulatory DNA.
A regulatory sequence is a segment of a nucleic acid molecule which is capable of increasing or decreasing the expression of specific genes.
one million bases
In this case, that is a very significant distance...
The results have sometimes surprised her
This is important because it shows the significance of going into an experiment with an open mind, willing to accept that a hypothesis may be refuted.
98% of the human genome does not code for proteins
Why is this? What purpose does it serve?
field.
The diagram to the right is interesting because it shows that despite the accessibility of this technology, of course, some areas of the world simply do not have the proper resources.
Sometimes it is difficult to work out whether an unexpected result arose because a method did not work well, or because the epigenetic mark simply doesn't matter in that particular cell or environment
This is suggesting that other variables could be the reason for the "broken scissor" technique?
amenable
Capable of being acted upon in a particular way. (To the scissor approach.)
The tools need to be refined
CRISPR technology is far from perfect and must be tested further and improved upon before it can reach its full potential.
Addgene so that other research groups could use it — and they quickly did
A great example of researchers sharing their findings and information through Addgene.
confirming that the system worked
Really, it just provides strong evidence that the system worked.
to histones using the broken scissors to carry enzymes to specific spots in the genome
This refers to a previous portion of the article, in which they describe the possibility of "breaking" the scissors to simply make a gene impossible to express.
acetyl
This compound is C(O)CH3, derived from acetic acid.
we haven't had the kinds of tools that geneticists have had
This is a problem that is currently being tackled by Addgene! By providing tools and free information about CRISPR, Addgene allows more researchers to have access to the tools they need.
But without the ability to alter the marks at specific sites, researchers are unable to determine whether they cause biological changes
While it is possible (and even unavoidable) for the DNA to be opened or closed off, we lack the ability to determine where the DNA is changed... at least, without CRISPR-Cas9
environment shifts
A relevant example of a changing environment is when tadpoles mature and develop, allowing them (as frogs) to walk on land.
histones
Any group of basic proteins found in chromatin.
The best way to control gene activity, she thought, was to adjust the epigenome, rather than the genome itself
Epigenomes are groups of chemical compounds that can tell the genome what to do; By adjusting the epigenome, you can (according to this theory) indirectly adjust the genome itself.
tack
This means she changed her approach.
cell's metabolic machinery into a biofuel factory
This analogy is saying that by editing a cell's genetic material at multiple cites (in one cell), biologists can rewrite its function to change its behavior?
That combinatorial power
I believe this is referring to the ability of the CRISPR-Cas9 technology to target multiple genes in one experiment.
Lim thinks that the system can handle up to five operations at once. The limit, he says, may be in how many guide RNAs and proteins can be stuffed into a cell. “Ultimately, it's about payload.”
To rephrase this (I found it unclear), Lim is saying that CRISPR can target a maximum of (an estimated) 5 genes to edit. This is simply because we cannot yet fit the Cas9 enzymes into enough guide RNA's to edit more than 5 sites in one cell.
motifs
motifs are short, recurring patterns in DNA that are presumed to have a biological function.
Weissman
While the above diagram cannot be annotated, it provides a simplistic explanation of CRISPR-Cas9 technology. Each step is shown. It is important to note the example that shows how "hacking" allows genes to be turned off, not cut out.
“RNAi is a shotgun with well-known off-target effects,” he says. “CRISPR is the scalpel that allows you to be more specific.”
This section does a good job of comparing the two techniques. Put differently, it highlights the unpredictability and inaccuracy of RNAi compared to the exact precision of CRISPR (which consistently can be used to target any given gene).
neurodegenerative conditions
these are a variety of conditions which mostly affect the neurons in the human brain. They are often results of affected neurons in the spinal cord (key to the central nervous system).
toxic protein aggregates
"toxic protein aggregates" refers to a biological phenomenon in which mis-folded proteins clump together, often resulting in severe disease (for example, Parkinson's or Alzheimer's).
guide RNA
RNAs that guide the insertion or deletion of uridine residues into mitochondrial mRNAs. They are used in CRISPR-Cas9 technology to take the Cas9 enzyme to the desired gene, so that it slices a specific portion of the DNA, rather than targeting genes at random.
hundreds of different cell lines
Cell lines are cell cultures that developed from a single cell. They therefore are made of cells with a uniform genetic makeup.
(see 'Hacking CRISPR').
The term "hacking" has been used multiple times so far. In this context, it means tweaking the CRIPR techniques to have different results (such as turning on and off genes).
they had built a way to turn genes on and off at will
This is groundbreaking because it is a comparatively simple, efficient, and cost-effective method of editing gene expression.
the enzyme stalled there and blocked other proteins from transcribing that DNA into RNA
This is another way of saying it stopped the expression of the gene. This is important because it allows biologists to turn off genes without the risk of causing accidental mutations (like previously described).
we broke the scissors
This metaphor means that the team altered the Cas9 enzyme so that it could only stop the target gene from being expressed; it does NOT cut it out (similar to Knock Out versus Knock Down).
hobbled
In this case, "hobbled" means that the protein of gene is having its function hampered or impeded.
a minor error introduced during repair can completely alter the sequence of the protein it encodes, or halt its production altogether
One small mistake can result in a genetic mutation, but could also make no significant change in the genetic code/DNA. It is almost impossible to predict, and therefore "mistakes" in DNA repair can be helpful in displaying the role of various genes (what exactly they do).
Cas9 enzyme
Cas9 enzymes are RNA-guided DNA endonuclease enzymes, which are used in CRIPR to locate and cut-out the desired gene.
snips through DNA like a pair of molecular scissors
This metaphor highlights how biologists can target genes and simply cut them out and (if they desire) replace them.
tinker
This word stands out to me because it seems playful and even unprofessional. It comes back to the idea that this new gene editing technology is truly fun and exciting.
Nature
Nature is an extremely respected scientific journal (the most cited scientific journal in the world). Nature has been focusing largely on CRISPR-Cas9 technology and is a common platform for information and updates about the subject, targeting research scientists as their audience.
“It's just so fun.”
This is an attitude that many scientists working with CRISPR share; the possibilities and applications of the technology are groundbreaking and "fun" to experiment with!
haematologist
Haematologists study the blood and blood-forming tissues, often focusing on the diagnosis of blood-born disease and disease in the bone marrow.
Scientists are hacking the tools so that they can send proteins to precise DNA targets to toggle genes on or off
In the past decade, dozens of experiments have tested the possibility of accurately slicing pre-determined genes for the purpose of removing them and even replacing them with more desirable genes.
its potential for treating disease or editing the genes of human embryos
A surprising amount of controversy surrounds this potential, because of the argument of ethics. One of the linked articles discusses the argument that editing human genes to reduce the chances of birth defects or genetic disorders is immoral and has the potential to become discriminatory.
Addgene has sent 60,000 CRISPR-related molecular tools — about 17% of its total shipments — to researchers in 83 countries, and the company's CRISPR-related pages were viewed more than one million times in 2015.
While Addgene primarily ships plasmids to international buyers, their website explains exactly how CRISPR technology works, and how people who are new to the field can get involved.
to slice the genome in human cells at sites of their choosing
Feng Zhang, a leading gene-editor at MIT and Harvard, successfully adapted CRISPR-Cas9 for genome editing in eukaryotic cells for the first time in January of 2013.
We get calls within minutes of a hot paper publishing
This shows the importance of Addgene in the CRISPR field; Addgene is dedicated to informing the public about updates with CRISPR technology, as well as assisting in the progress of the gene editing practices.
reagents
reagents are substances that are used in chemical analysis or other reactions. A common example of a reagent is sulfur.
Addgene
Addgene is a non-profit organization that offers cloning data and plasmids to laboratories across the globe. Founded in 2004, Addgene also runs a free online database for information about plasmid cloning.