Oh on the other hand I didn't notice the cancer part.
To get into my course I actually had to do a presentation about a laser assisted vaccine which used vaccibodies to stimulate immunity against melanoma.
Anyway there are a few cancers that can be cured, either by surgery, radiotherapy or sometimes pharmacology (Provenge for example). I think Glivec was the first treatment developed against Myeloid Leukemia. There are vaccines too (for CMV for example)
Providing a cure for all cancers is very difficult because there are various kinds that have different properties.
One possibility that is being explored is the ability to prevent angiogenesis. It's the remodelling of vessels to create new vessels to vascularise a certain part of the body, and because of their very high activity cancer cells often stimulate angiogenesis which is necessary to provide the nutrients allowing their growth. So people are trying to see if they can stop it to prevent growth and have easier surgeries.
There's also a thing on trial, which is basically a toxic but non diffusible molecule that can be induced by an external stimuli that would be injected into the blood and that would recognize an epitope often expressed by cancerous cells. Because of their high vascularisation they will be delivered massively towards cancer cells. Then you wait a few hours to have the non bound molecules excreted. Then you activate the bound ones which should cause the destruction of the tumors they are bound to. (it's a very simplified explanation but the important part is here).
Another frustrating thing we have currently is that a lot of brain tumors/cancers respond to molecules that we have developed, however these molecules cannot reach the brain because of the hematoencephalic barrier so we can't treat these tumors. There's a team in Harvard which is trying to develop a technique that would use ultrasounds to temporarily disrupt the barrier so that you can administer the drug in the meantime, but it has to be short enough to not be detrimental to the brain cells. It seems pretty promising if you ask me (I'd like to go for an internship in their lab )
But most of the time I simply call anything that moves on rails a train without making any difference
So as to not be out of subject gonna talk a bit of Rett Syndrome since the lab director I saw wants me to work on something related to it.
It's a genetic disease that only affects young girls. In fact it's because the gene responsible for the disease, MECP2, is located on the X chromosome, so boys who have a mutated version die before birth. It's a gene that play a part in regulating the transcription of other genes, including those which lead to the production of KCC2. KCC2 is a transporter which plays a role in creating asymmetry in the repartition of chloride ions between two sides of the membrane of neurons. So not going to explain the Nernst equation and all but basically this asymmetry plays a role in their fluxes when specific canals open. Usually chloride ions are "too" concentrated on the outside and will get inside the cell when the canals are opened which causes inhibition. When KCC2 is dysfunctional the extracellular chloride concentration is too low, therefore inhibitory synapses cannot function properly and chloride may even tend to get out of the cell, therefore leading to a stimulating activity. KCC2 also has another role which was demonstrated by this team recently, it interacts with proteins from the cytoskeleton (as the name suggests it's something that acts as a skeleton for the cell, except that it's also very dynamic) and plays a role in regionalisation of membrane receptors. It's particularly important because the "weight" of each synapse (the place where one neuron transmits information to the next one) is modulated by activity, and in particular in the case of glutamatergic signaling (glutamate is a neuromediator) a process called LTP was evidenced. The receptors are actually not immobile, there is a constant control of their position and they can be taken away or added to a synapse to make it weaker or stronger, depending on its activity. All these processes seemingly need a functional KCC2 in some parts of the hippocampus.
So the young girls who suffer from this disease usually undergo a regular development up to two years, but starting from then they begin to regress and suffer from crippling psychomotor troubles. The team is interested in knowing if administering drugs that help control chloride concentration is useful or not. Their hypothesis is that it's not and that the troubles are due to the impaired LTP. So what he told me I could do is try to express various kinds of mutants of KCC2, quantify them relatively to sound cells to see that they are correctly expressed etc. Then the point would be to use a marker that allows us to determine intracellular chloride concentration. The goal is to find a protein that is integrated in the membrane, interacts with the cytoskeleton correctly but cannot do its role of chloride transporter. Then we'd do the same thing in a mouse model and conduct experimental tests to see if it has Rett syndrome symptoms or not.
If the hypothesis is correct it should have less important symptoms, so giving people who suffer from this disease things like diuretics is useless and work should be put on rescue procedures (though rescue is pretty hard to put into place).
In fact I was pretty enthusiastic about that and wanted to share
Anyway bringing up the X chromosome makes me think that an explanation about lyonisation and epigenetics in general may be interesting. Anyone ever wondered why, even though all our cells have the same DNA, a neuron is very different from a muscle cell which is very different from an adipose cell?
More seriously I don't really know how the thread is meant to work because from what I understood it was more a things to post links. But I was pretty excited about Rett Syndrome and I thought it might be fun to see how people are doing their job behind the scenes.
Exactly. Extremely interesting. I had no clue how many nerves we had down there.
Why isn't the video loading for you?
Yup, discuss anything medical related.
You developed very well the " pathophysiology " side of the disease, which was fascinating to read ( particularly the cotransporter KCC2, his role and his function ^^ )
But I am more interested about the " physical findings " of the patient which suffer from the cerebroatrophic hyperammonemia ( RS )
Hmm, so basically, restoring KCC2 function in Rett neurons may lead to a potential treatment for Rett syndrome ?
Last edited by Akira; 02-19-2016 at 12:10 AM.
Check that site down. Might be basic for some of you guys, but it's a pretty good site.
Weird name for it
Went around quickly and they actually develop things about the cytoskeleton mitochondria etc. Yes it's pretty basic but it's pretty well explained at the same time, good site
So yep I talked about this site to @Akira
Unfortunately I don't think they're in english, though some slides are but it may be of interest to those who can understand french.
There are actually various topics dealt with by the way, there are also maths or physics courses, and things about history anthropology etc
Do you guys know anything about optogenetics? Sees like an interesting concept.
Yes. There's a coupling that goes between the channel being lit and it letting something go through it.
I think the first one that was used was Bacteriorhodopsin (if I'm not mistaken it's been used for quite some time, Racker and Stoeckenius used it around 1975 I think but for something else entirely).
It's capable of pumping an H+ when it's lit at a given wavelength. Well actually it's not a pump but a "mere" channel, as the ions it lets through can only flow in the sense of their electrochemical gradient (don't know if you're familiar with the rules that dictate the flow of species on each sides of the membrane).
Then someone though that if you could express the gene of the protein into someone its cells would have a channel activated by light. They refined it to put that expression under the control of specific promoters, that are only active in some subtypes of cells (for example you can have it expressed only in GABA neurons and another one in Glutamate neurons). Since the activity of neurons is dictated by ions flows that allows you to control their activation.
And then they decided to refine it even further to be able to use different colors/wavelength to activate various channels so as to be able to act on closely packed populations of neurons and only activate on population. For example Chronos is activated by blue light while Chrimson is activated by red light.
There is extensive research to modulate the kinetics and the absorption specters of the channels to avoid spectral cross talk etc, that is/was one of the main axis of Ed Boyden's lab in MIT.
I think (but that's more an hypothesis) that it relies on messing with links that have redox properties (like retinol or DNA photolyase which use either double links or something like flavine to couple energy from light and a movement of a biological structure)
Tried to summarize the whole thing if others are interested too, hope I still answered correctly
Last edited by Dai Don Dedede; 02-24-2016 at 04:09 PM.