gene transcription

The mysterious powers of spider silks

Spider silks, the stuff of spider webs, are a materials engineer’s dream: they can be stronger than steel at a mere fraction of weight, and also can be tougher and more flexible. Spider silks also tend not to provoke the human immune system. Some even inhibit bacteria and fungi, making them potentially ideal for surgery and medical device applications. Exploitation of these natural marvels has been slow, due in part to the challenges involved in identifying and characterizing spider silk genes, but researchers from the Perelman School of Medicine at the University of Pennsylvania have now made a major advance with the largest-ever study of spider silk genes.

As they report today in an advance online paper in Nature Genetics, Penn scientists and their collaborators sequenced the full genome of the golden orb-weaver spider (Nephila clavipes), a prolific silk-spinner that turns out to produce 28 varieties of silk proteins. In addition to cataloguing new spider silk genes, the researchers discovered novel patterns within the genes that may help to explain the unique properties of different types of silk.

Keep reading

Seeking SciNote, Biology: CRISPR

Question:

What do geneticists think will be possible when the the new gene-splicing CRISPR is fully operational on patients?

Answer:

For those of us unfamiliar, CRISPR is a revolutionary new genetic splicing technology. Gene splicing refers to modifications to a gene transcript that can result in different proteins being made from a single gene. Interestingly, CRISPR’s inception began when dairy scientists discovered that bacteria used to create yogurt (by transforming lactose into lactic acid) had incorporated snippets of benign viruses into its genome. To their surprise, the incorporated DNA would create toxic agents to thwart infective viruses. In 2007, dairy scientists realized that they could effectively fortify bacteria by adding spacer DNA, which does not code for any protein sequence, from a virus. Then, five years later, as Time Magazine writer Alice Park skilfully describes, professors Jennifer Doudna and Emanuelle Charpentier noticed “up to 40% of bacteria developed a particular genetic pattern in their genomes. What they found were sequences of genes immediately followed by the same sequence in reverse, known as palindromic sequences. Further, bits of random DNA bases cropped up after each such pairing and right before the next one. After the dairy bacteria transcribed its spacer DNA and palindromic sequence into RNA, it self-spliced those segments into shorter fragments, with an enzyme called CAS9”. As you may be wondering, CRISPR stands for “clustered regularly interspaced short palindromic repeats”.

It is important for us to emphasize the versatility of this method. In the 2007 article, Doudna and Charpentier go into depth regarding the many benefits of the new genetic technology. These include the potential to “systematically analyze gene functions in mammalian cells, study genomic rearrangements and the progression of cancers or other diseases, and potentially correct genetic mutations responsible for inherited disorders”. As you might imagine, this opens up possibilities that were previously science fiction. Currently, painful blood transfusions are commonplace in the treatment of many diseases such as sickle cell anemia. Sickle cell affects red blood cells, which are made by stem cells in bone marrow. Soon, Massachusetts Institute of Technology synthetic biologist Feng Zhang envisions that this will soon no longer be necessary. She predicts that after doctors extract some of the marrow, scientists will splice out the defective fragment of DNA using CRISPR from the removed stem cells, then bathe the cells in a solution containing the non-sickle-cell sequence. As the DNA repairs itself naturally, it picks up the correct sequence and incorporates it into the stem cell genomes. After this one-time procedure, the stem cells would give rise to more red blood cells with the healthy gene. Eventually, the blood system would be repopulated with normal cells.


The treatment of HIV using CRISPR would be very similar. In this potential treatment, “patients would provide a sample of blood stem cells from their bone marrow, which would be treated with CRISPR to remove the CCR5 gene, and these cells would be transplanted back to the patient. Since the bone marrow stem cells populate the entire blood and immune system, the patient would eventually have blood cells that were protected, or “immunized,” against HIV”.


Despite this extraordinary potential, no biological technology comes without serious ethical concerns. As Jennifer Douda says herself, CRISPR “really requires us to careful thought to how we employ such a tool: What are we trying to do with it, what are the appropriate applications, how can we use it safely?”

Check out her book The Stem Cell Hope for learning about the future of stem cell technology.

Sources:
Park, Alice. “A New Gene-Splicing Technique.” 100 New Scientific Discoveries: Fascinating, Unbelievable and Mind-expanding Stories. New York, NY: TIME, 2014. 92-95. Print.

Park, Alice. “It May Be Possible To Prevent HIV Even Without a Vaccine.” Time. Time, 6 Nov. 2014. Web.

Doudna, Jennifer A., and Charpentier, Emmanuelle (2014). The new frontier of genome engineering with CRISPR-Cas9. Science, 346(6213), 1258096–1258096. doi:10.1126/science.1258096

Answered by: Teodora S., Expert Leader and Expert John M.

Edited by: Carrie K.

DNA Replication & Repair

Remember!!! Inactivation of tumor suppresor genes fuck up DNA repair. Examples:

  • p53: prevents damaged DNA to enter S phase. Deletion or Inactivation = LiFraumeni Sd.
  • ATM gene: encodes a kinase for p53 activity. Inactive: Ataxia Telangectasia.
  • BRCA-1: breast, prostate, ovarian cancer
  • BRCA-2: breast cancer
  • Rb gene: negative regulator, binds TF-E2f & repress transcription of genes required in S phase. Inactive or deletion = Retinoblastoma, Osteosarcoma.
Mutating the switches

Gene transcription is complicated. The process of making RNA copies of stretches of DNA requires a large number of proteins attaching to and interacting with the genetic material to get the ball rolling. These proteins attach to the DNA at promoter sites near the start of genes, and other more distant control regions called enhancers. Both of these areas are known as regulatory regions, or genetic switches, and are used to turn gene expression on and off to meet the needs of the cell.

According to a couple recent studies published in Nature, these collections of proteins that gather around promoters and enhancers make these genetic switches more prone to lasting mutation than the surrounding DNA by blocking the action of the cell’s repair crew.

Mutations happen all the time as you are exposed to carcinogens throughout your day. For example, just spending an hour in the sun causes about 80,000 mutations in each cell. Fortunately, your cells come with an expert DNA repair team that runs around the nucleus fixing damage as fast as it happens. Occasionally, they miss a spot, and the mutation sticks, affecting all future generations of that cell. If the mutation is in a critical gene or control area, the cell can start to divide uncontrollably, resulting in cancer.

When access to the DNA is blocked by proteins gathering to turn a gene on or off, the repair crew can’t get in to fix damage caused by factors like UV radiation. Both groups of researchers analyzed mutation rates along strands of DNA from cancer cells, and found that some of the highest mutation rates occurred right in the middle of these regulatory regions. This means that mutations aren’t being fixed by the repair team nearly as often as they should.

This is important in understanding how cancers form initially. Mutations in the regulatory regions can cause the on-off switches to lose their function, and genes that should be tightly controlled by the cell could be either on or off all the time. At this point of the research, it isn’t clear what we might be able to do about these “protected” mutations, but every bit of knowledge about how cancer gets started could help us find better ways of treating and preventing this horrible disease.

References and further reading

Hard-to-reach repairs, Ekta Khurana, Nature, 4/14/16, p 181

Differential DNA Repair underlies mutation hotspots at active promoters in cancer genomes,Dilmi Perara et al, Nature, 4/14/16, p 259

Nucleotide excision repair is impaired by binding of transcription factors to DNA,Radhakrishan Sabarinathan et al, Nature, 4/14/16, p 264

DNA Damage & Repair: Mechanisms for Maintaining DNA Integrity, Suzanne Clancy, Scitable,2008


Image credit: Wikimedia user Forluvoft, public domain

16th october 2015 : i’m officially halfway through my first semester ! it’s been a long ride and i’ve gotten in 3/6 of my subject internal assessments for the IB and after the holidays, we still have a couple more to go, as well as my Extended Essay final copy and my first TOK essay draft due in ~ and on top of that, i have revision to do since we have a round of mock exams in 12-13 weeks time.

probably one of the things i need to prepare for the most is Biology HL so here i am, familiarising myself with the concepts for dna replication/transcription/translation/gene expression and other key biological process. im going to be doing much more of this over the half-term holidays.

Long-term potentiation and Long Term Depression

I can’t emphasize to y’all how angry I am that I didn’t make a post about LTP. Like. I could have sworn I did? It’s pretty much the best understood pathway for learning and cognitive flexibility how could I not have done that. Anyways, here it is.I just made a half assed powerpoint presentation so y’all best be greatful.

Glutamate has 3 ionotropic receptors, Kainate, NMDA, and AMPA. I only care about NMDA and AMPA right now, because thy have a fascinating relationship. NMDA pretty much requires AMPA to be active in order to activate, and here’s why.

Hello, yes, I’m a paid scientist and this is my shitty infographic. AMPA,  on the right, is a pretty basic ionotropic receptor. Something will bind, and an ion will pass. NMDA has more bells and whistles. It requires the binding of  both glycine and glutamate, but this is really just a formality since glycine is so abundant in these brain regions that one is almost always bound to the receptor. The important part is that magnesium ion bound within the channel.

Say, theoretically, glutamate did bind, well, that’s nice, but nothing is going to happen. The Mg2+ ion acts as an allosteric antagonist, preventing passage of Ca2+ and Na+. (Here’s a link to my post about antagonists if you’re wondering what that is). So ok glutamate and glycine doesn’t do it, what exactly does it take to activate NMDA? Well… to answer that, we’re gonna have to talk about AMPA now.

AMPA is an ionotropic receptor that transmits Na+ via the binding of glutamate alone, and once Na+ enters the cell, it causes a slight depolarization of the cell membrane…

… Dislodging the magnesium in NMDA! (the cell membrane has become too positive for Mg2+ so it just peaced out). Now Ca2+ and Na+ can enter! The Na+, of course, further depolaries the cell causing an action potential, but the Ca2+ acts as a second messenger in the cell, upregulating gene transcription of… AMPA (and other proteins for increased dentritic spine density)! So it’s like AMPA gave NMDA the extra boost it needed to activate, and to return the favor, NMDA told the cell to make more of its friend AMPA.

These two have a relationship called the coincidence factor, and it functions much like classical conditioning, which is pretty much why it’s everyone’s favorite thing. So you have a unconditioned stimulus, unconditioned response, conditioned stimulus, and conditioned response. 2 things need to happen at the same time to form a memory (i.e. strengthen a synapse). You need an action potential along the cell membrane AND glutamate binding. So let’s say one of these is the unconditioned stimulus… Cell depolarization, in this case. The unconditioned response is an action potential. Now we have glutamate paired with this as the conditioned stimulus, which as we know, alone doesn’t cause an action potential. However, if this happens enough, enough Ca2+ will enter the cell creating enough AMPA receptors (which require only the binding of glutamate) to allow for the BOTH to alone cause an action potential. We also now have a bunch of AMPA receptors, leading to a strengthened synapse, meaning this is a memory, a pairing, we want to keep.

So back out of the biology for a second and think in leyman’s terms. Say the smell of food caused an action potential along a cell membrane (leading to salivating). And say a whistle caused glutamate release in the synapse (leading to nothing). If these happen at the same time, according to classical conditioning, eventually the whistle would cause an action potential without the presence of food (salivating). So that’s a bit of biology behind one of the best understood theories of memory.

NOW there’s also long term depression with NGL I know very little about other than it is the weakening of this connection and a disassociation so eventually the whistle would no longer cause salivation kind of thing. How and when this happens is beyond me at the moment. Let me know if you know.

A variation of the “Brainbow” gene adds a transcriptional “roadblock” to inhibit expression of the fluorescent proteins until Cre is activated. By placing Cre under the control of a tissue-specific promoter, the “Brainbow” effect can be activated in one tissue of the mice. This is called the “Confetti” mouse.

Image: Here the “Confetti” gene is transiently activated in all liver cells in a mouse ~4 weeks of age. As a result, each cell independently recombines the “Confetti” gene toward one of four fluorescent proteins. Image was taken after 2 months tracing with a Leica SP5 microscope; 10x objective.

Our closest wormy cousins: About 70% of our genes trace their ancestry back to the acorn worm

A team from the Okinawa Institute of Science and Technology Graduate University (OIST) and its collaborators has sequenced the genomes of two species of small water creatures called acorn worms and showed that we share more genes with them than we do with many other animals, establishing them as our distant cousins.

The study found that 8,600 families of genes are shared across deuterostomes, a large animal grouping that includes a variety of organisms, ranging from acorn worms to star fishes, from frogs to dogs, to humans. This means that approximately 70% of our genes trace their ancestry back to the original deuterostome. By comparing the genomes of acorn worms to other animals, OIST scientists inferred the presence of these genes in the common ancestor of all deuterostomes, an extinct animal that lived half a billion years ago. This research shows that the pharyngeal gene cluster is unique to the deuterostomes and it could be linked to the development of the pharynx, the region that links the mouth and nose to the esophagus in humans. These findings were published in Nature, summarizing an international collaboration between OIST researchers and teams from the US, UK, Japan, Taiwan and Canada.

Around 550 million years ago, a great variety of animals burst onto the world in an event known as the Cambrian explosion. This evolutionary radiation revealed several new animal body plans, and changed life on Earth forever, as complex animals with specialized guts and behavioural features emerged. Thanks to the genome sequencing of multiple contemporary animals of the deuterostome group, we can go back in time to unveil aspects of the long-lost ancestor of this diverse group of animals.

Acorn worms are marine creatures that live on the ocean floor and feed by filtering a steady flow of sea water through slits in the region of their gut between mouth and esophagus. These slits are distantly related to the gills of fish, and represent a critical innovation in evolution not shared with animals like flies or earthworms. Since acorn worms occupy such a critical evolutionary position relative to humans the researchers sequenced two distantly related acorn worm species, Ptychodera flava, collected in Hawaii, and Saccoglossus kowalevskii, from the Atlantic Ocean. “Their genomes are necessary to fill the gap in our understanding of the genes shared by the common ancestor of all deuterostomes,” explains Dr Oleg Simakov, lead author of this study.

Indeed, beyond sequencing these two organisms, the team was also interested in identifying ancient gene families that were already present in the deuterostome ancestor. The team compared the genomes of the two acorn worms with the genomes of 32 diverse animals and found that about 8,600 families of genes are homologous, that is, evolutionarily-related, across all deuterostomes and so are confidently inferred to have been present also in the genome of their deuterostome ancestor. Human arms, birds’ wings, cats’ paws and the whales’ flippers are classical examples of homology, because they all derive from the limbs of a common ancestor. As with anatomical structures, genes homology is defined in terms of shared ancestry. Because of later gene duplications and other processes, these 8,600 homologous genes correspond to at least 14,000 genes, or approximately 70%, of the current human genome.

The study also identified clusters of genes that are close together in acorn worm genomes and in the genomes of humans and other vertebrates. The ancient proximity of these gene clusters, preserved over half a billion years, suggests that the genes may function as a unit. One gene cluster connected with the development of the pharynx in vertebrates and acorn worms is particularly interesting. It is shared by all deuterostomes, but not present in non-deuterostome animals such as insects, octopuses, earthworms and flatworms. The pharynx of acorn worms and other animals functions to filter food and to guide it to the digestive system. In humans, this cluster is active in the formation of the thyroid glands and the pharynx. Scientists suggest there is a connection between the function of the modern thyroid and the filter feeding mechanism of acorn worms. This pharyngeal gene cluster contains six genes ordered in a common pattern in all deuterostomes and includes the genes for four proteins that are critical transcriptional regulators that control activation of numerous other genes. Genes ordered in the same way and located next to each other in the chromosomal DNA are linked and transferred together from one generation to the next. Interestingly, not only the DNA that codes for these transcription factor genes is shared among the deuterostomes, but also some of the DNA pieces that are used as binding sites for the transcription factors are conserved among these animals.

“Our analysis of the acorn worm genomes provides a glimpse into our Cambrian ancestors’ complexity and supplies support for the ancient link between the pharyngeal development and the filter feeding life style that ultimately contributed to our evolution,” explains Dr Simakov.

Recently, the OIST team also sequenced the genomes of the octopus and the coral Porites australiensis.

Image: This is a juvenile of Saccoglossus kowalevskii with one of the transcription factors expressed in the pharyngeal region (highlighted in blue).

Credit: Andrew Gillis

anonymous asked:

Why are you opposed to captive hybrids? If the female were artificially inseminated, would that change your opinion? (I don't keep reptiles (or amphibians) but dogs, for example, are frequently crossed and that tends to make them less prone to genetic diseases so I was wondering why it was such a no no for reptiles. Other than dog/wolf hybrids which are healthy but problematic for other reasons.)

Dogs are crossed to different lineages of their own species. Dogs and wolves are the same species, albeit separated by several thousand years of human domestication (dogs were first domesticated around 15,000 years ago). Dog/Wolf crosses are not hybrids.

People crossing snakes are doing it across distantly related species, occasionally belonging to different genera even (read: millions of years of difference). This is not suring up their genetics. Hybridisation of this kind is likely to turn up problems because the mitochondria is only suited to one of the chromosome sets (the maternal chromosome), and this can raise problems in gene transcription. It also is more likely to produce genetic incompatibility across the genome. Hybrids may be more susceptible to disease, as is known from ligers. Or they might have weird chromosome numbers, because reptile chromosomes behave strangely sometimes.

Just because two things can interbreed does not mean they should. The chance of defects is high, and it is not worth toying with the lives of animals to see what happens.

anonymous asked:

Can you please explain how electron orbitals work? Like what are they why are they all weird shaped and what the heck are nodes? Also- bonus question: clarify how electrons act like waves and particles

I’m not a quantum chemist in any way shape or form, and I failed pretty hard at doing basic tasks like making buffer today so I may not be the best source of information here, but I’ll do my best to answer your question.

Atomic orbitals are probability density functions, which means that they represent the area where an electron is most likely to be found, (if you want to think of an electron as a discrete particle with a definite location, which isn’t actually accurate but is a nice approximation that makes everybody’s head hurt a little less, so let’s go with that.) The nodes then, are the places that the electron is definitely not, like never ever. A handy way to remember this is nodes = No damn electrons. 

The shapes happen because orbitals behave like waves, so they add and subtract from each other based on their signs (positive and negative, not pisces and gemini, the reason that they have said signs is as mysterious to me as why people care about the zodiac, but has more math involved).

This bit is pretty opaque to me because I spend my days thinking about things like gene transcription and worm genetics and not quantum mechanics, but basically each orbital is described by a set of quantum numbers denoting energy (n), angular momentum (l), axial (?) orientation (ml) and spin (ms), which taken together describe their shape and size based on the Schroedinger equation, but the one that is most important for the shape is angular momentum (l). Why they are shaped the way they are is due to the way that the Schroedinger equation is solved for those numbers and has to do with oscillations and shit, iirc, but basically if you do the math it makes sense. If not, you accept that they look the way they do and don’t judge the d and f orbitals for their weird shapes. 

(mj-the-scientist could probably explain all of this better because this is sort of her field, so yeah, please correct my many mistakes, I am a humble biologist)

As for why electrons (and all particles really) act as both waves and particles? The best allegory I’ve got is this:

It’s like how science-jesus is both fully human scientist and fully divine scientist while also only one single scientist. The way that that adds up has been the subject of much ecclesiastical debate, has lead to schisms in the science church, and makes your head hurt if you think too much about it, but is ultimately because a bunch of old guys said so a long time ago. In our case, the old guys are math.