Genetic Engineering stuff

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Genetic Engineering stuff

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1DugsBooks
Giu 17, 2018, 7:25 pm

I thought I would start a new topic with a generic title, not really educated enough to be more specific.

I was really struck by this article in Science about some recent advances in learning how those Planarian worms can grow new or two heads etc. to repair almost any injury. Hope it is not pay walled.

Though often no bigger than an apple seed, planaria are the envy of the animal kingdom. Cut them into a dozen pieces, and each piece will regrow into a full new worm—a remarkable feat of regeneration beyond the ability of most other animals. Now, researchers have pinpointed the cell—and a key protein—that kick-starts this process.

http://www.sciencemag.org/news/2018/06/one-newly-discovered-cell-can-remake-whol...

2stellarexplorer
Giu 18, 2018, 1:54 am

Fascinating. You know this area will continue to explode (as it is in cancer genetics) now that we have the tools to really delve into what is happening in cells at the level of genes and gene regulation. So far, I’m enjoying the ride. But the last ten years will be as nothing compared to the next several decades.

3krazy4katz
Giu 18, 2018, 1:39 pm

Also in retinal degeneration. Even fish can regenerate the cells that detect light but mammals cannot.

4DugsBooks
Modificato: Giu 27, 2018, 10:32 am

>2 stellarexplorer: "You know this area will continue to explode" - exactly! Both fields are so intricately detailed and complex as mechanisms are worked out for {genome derived}* data driven inferences that my mind can not wrap around a lot of it {my incomprehension not of great import of course} and I have to think that computer AI's are going to have to be integrated into the process. I bet just staying up to date in any field is very taxing and some AI will be needed to run through all the research and throw out some time saving suggestions.

* edited in.....I keep seeing statistical inferences drawn from genome evaluations

5stellarexplorer
Giu 23, 2018, 2:02 am

>4 DugsBooks: Yep, that seems like a good inference. I suspect that the same could be said for many fields. At the risk of repeating my post above, we are also at the very beginning of seeing where AI will take us. AIs may process and “think” in ways so different from the human that it is hard to anticipate where it’s heading. I just hope that the AI worriers are overworrying.

6BTRIPP
Giu 23, 2018, 6:24 am

7stellarexplorer
Modificato: Giu 24, 2018, 12:50 am

>6 BTRIPP: I saw that too, but as long as we are getting on to one of my favorite topics, human origins, let me recommend this:

http://science.sciencemag.org/content/360/6395/1296.full

It’s typical of the reconsideration made necessary by the emerging genetic understanding of the mixing of H sapiens with Neanderthal and Denisovan populations in Eurasia, and the way that has given new life to the previously (now prematurely) discredited multiregional model of our ancestry, as opposed to the recently out of Africa or ROA model that had gained ascendency since the 1980s.

I haven’t mentioned in this group that I am 1-2 weeks from going public with my new YouTube channel, in which I want to present an ongoing series of videos that cover a range of topics of fascination to me, hopefully entertaining as well. I want these videos to have a broad focus, but because of the significant way genetics is overturning previous understandings of human origins and human migrations, I will be very tempted to focus a lot of attention on these issues.

I guess I’ll announce the channel in a thread in this group in case anyone is interested in watching/subscribing. I have four completed videos at present.

8DugsBooks
Giu 23, 2018, 6:34 pm

>7 stellarexplorer: Look forward to checking it out.

9DugsBooks
Modificato: Mar 15, 2019, 5:11 pm

Here is an article that is a continuation on >1 DugsBooks: I believe. Whole-Body Regeneration in Worms Directed by Gene Regulatory Network Here, as I understand it, they cut another type of worm in half that regenerates its entire body and measured what the chromosomes did in response as it regenerated.

Here is a quote summing up the article : "By viewing whole-body regeneration through an epigenomic lens, we uncovered a regulatory mechanism underlying dynamic gene transcription during regeneration," the authors concluded, noting that the same strategy "can be applied to established and emerging model systems to gain a deeper mechanistic understanding of the transcriptional cascades that underlie the phenomenon of regeneration."

Took me a while to read it - I had to look up many words and nearly every process mentioned to get an idea of what they were describing but it is interesting, kind of like a detective story as the they try to unravel a mystery and find another fact.

10stellarexplorer
Apr 9, 2019, 11:37 am

11DugsBooks
Apr 9, 2019, 4:55 pm

>10 stellarexplorer: Great link Stellar, the article makes the work a lot more accessible to folks like me I guess. Sounds exciting and stimulates the imagination when you wonder what developments might come of the research.

12krazy4katz
Apr 9, 2019, 8:33 pm

>10 stellarexplorer: Thank you! Great article! There is so much coming out about noncoding regions and epigenetic modifications. The genome used to be such a simple concept. Now it is a tangle.

13stellarexplorer
Apr 11, 2019, 12:48 am

>12 krazy4katz: Absolutely! And in humans, for example, that doesn't even count the genes in the gut microbiome which vastly outnumber the size of the human genome itself....

14reading_fox
Apr 11, 2019, 4:07 am

>12 krazy4katz: "The genome used to be such a simple concept. Now it is a tangle." welcome to science. The more you look the more you realise you don't understand. I'm not sure there are any simple concepts in biology.

15DugsBooks
Apr 23, 2019, 2:04 pm

Here is a quote I thought was interesting and related to regeneration - which I might do some follow up google searches on:

"The coast redwood is the second-largest genome ever sequenced. The largest belongs to the axolotl, a North American salamander whose genome has more than 28 billion base pairs, giving it a remarkable ability to not only regenerate limbs but also grow back internal organs, according to the researchers."

Maybe there are some advantages to quantity when it comes to genomes - I could use a few spare organs!

The quote from the San Francisco Chronicle article California scientists unravel genetic mysteries of world’s tallest trees

16krazy4katz
Apr 23, 2019, 9:40 pm

Yes even fish can do that — I don't know about all of them, but at least some. Lots of research going on to see if this can be replicated in humans. Imagine being able to do that!

17reading_fox
Apr 24, 2019, 5:29 am

>15 DugsBooks: absolute genome size is very random, with huge and tiny genomes scattered all over the species tree, sometimes varying considerably between closely related species. A lot of the size is thought to be 'junk' viral inserts, and mis-copied segments. https://en.wikipedia.org/wiki/C-value#Variation_among_species

So it's unlikely to be size per se that helps regeneration but some specific genes within that mix.

18stellarexplorer
Apr 24, 2019, 10:55 am

>17 reading_fox: True, it’s a specific property that the genes confer, not the size of the genome.

19DugsBooks
Modificato: Apr 25, 2019, 3:24 pm

>17 reading_fox: >18 stellarexplorer: Yep I have read those articles since the first human genome project about big chunks of "junk" DNA, I have also read recently a lot of articles about Epigenetics which show portions of the genome thought to be junk or not much known about being activated by environmental conditions. Just with probability the larger the genome you have the more chance of having something to be triggered by conditions - saying that but most of it could be just viral based junk stuff like is said.

::edited::

Seems like I also remember reading that large junk areas can be advantageous in that when the genome is changed by some event if the change happens in the "junk" area then no harm done.

20kurdziel
Apr 25, 2019, 9:47 pm

>19 DugsBooks: DugsBooks:
You are certainly correct—regions of the human genome once considered “junk” have turned out to be pieces we didn’t/don’t understand the purpose of. Now the research has become more focused on the function of the proteins the genes encode, and the role of RNA segments (transcribed from DNA, but not necessarily used to make its protein), transcriptomes (small molecules the control the transcription rate and/or whether the DNA is transcribed at all. The ability to edit DNA via the CRISPR technique has resulted in cancer treatments in which a known controlling gene sequence can be removed and replace with the correct sequence.
With newer technologies allowing us to view cellular mechanisms, gene amplifications/mutation, protein expression in its microenvironment have opened up a wide variety of studies focused on numerous pathways, cell interactions with other cells and the proteins which surround it. The most stunning discovery it the vast variability of the processes we assumed to be stable. We now know how little we know and are playing catch up in the nanoscale (10E-09 meters) environment where the laws of quantum mechanics apply.
Some of the most promising new cancer therapies involve modulation of the body’s immune system, specifically exploiting the fact that many tumors turn off the immune response (via “check-point inhibitors”). While many classical chemotherapeutics suppress immune response, newer strategies exploit the fact that our bodies create a targeted immune response to a tumor growing inside— by extracting blood cells that specifically target the specific tumor, growing larger amounts of these specific cells and injecting the now larger number of a patients own tumor targeted immune cells, (i.e. T-CAR) has result in remissions and potential cures in patients with hematologists malignancies (I.e. B-cell Lymphoma, leukemia)—while still in its infancy, these promising results have resulting in further exploration of immune response and exponentially exposed the number of critical players and numerous and changing roles of molecules within the microenvironment (likely soon to by called the nanoenvironment).
The more we learn, the less we know

21reading_fox
Apr 26, 2019, 4:52 am

>20 kurdziel: - Crispr not yet good for cancer - still too many unknowns. But it is theoretically possible to treat something like Huntingdons which is known to be a specific mutation in one region of dna (Huntingdons is particularly possible for Crispr because it's caused by an excess of repeat units, so all that's needed is to cut out some of the repeats. It becomes trickier if you have to cut and then replace with a corrected version, and obviously much more tricky if it's several different target areas)

Obviously the recent chinese case where the two infants were crisper'd too remove an HIV susceptible dna region show what can be done. But generally we need a lot more understanding of the whole genetic environment, as above before we start tinkering too much.

22justifiedsinner
Apr 26, 2019, 9:48 am

>21 reading_fox: The Chinese experiment on human infants failed, they altered the wrong genes. The researcher is now under criminal investigation.

23krazy4katz
Apr 26, 2019, 12:17 pm

>21 reading_fox: >22 justifiedsinner: I don't think they altered the "wrong" gene in that specific sense. They altered the gene that HIV uses to get into cells. However, that gene has a normal function (I forget what that is). Therefore, there could be negative effects of knocking it out that are unknown at this time.

24DugsBooks
Apr 26, 2019, 1:29 pm

>20 kurdziel: well written, thanks. I hope some new discoveries in immune response therapy for solid tumors come about soon. I have learned, the hard way, that they can be persistent.

25justifiedsinner
Apr 27, 2019, 7:41 am

>23 krazy4katz: He attempted to delete the CCR5 gene. In one baby only one gene was affected with a 15 bp deletion. Status of the other baby is unknown. Both babies are though to be mosaics, some cells changed others not.

26krazy4katz
Apr 27, 2019, 1:24 pm

>25 justifiedsinner: Thank you for the information. I knew some of it but not all of the details. So the problem was he didn't delete it early enough ensure that it was in all cells. Also if only one gene was affected, there might not be any influence on CCR5's actual function. If they are mosaics, it gives one hope that it might not be passed down to the next generation, unless they already checked the reproductive cells in the babies. Perhaps this will turn out OK for the 2 children.

27justifiedsinner
Apr 27, 2019, 5:12 pm

>26 krazy4katz: The problem is that the cells are dividing as he is treating them. It may not be possible to treat them fast enough to stop them being mosaics. They still do not know if other genes have been inadvertently altered although the researchers claims that the mutations found are all naturally occurring ones.

28Taphophile13
Apr 27, 2019, 5:24 pm

As is usually the case, any change in one thing can have unexpected effects elsewhere. A deletion of CCR5 may give resistance or immunity to HIV but it may increase the risk of abdominal aortic aneurysm or complications from other viral infections.

https://blog.kittycooper.com/2019/01/are-you-genetically-resistant-to-aids/#more...

29DugsBooks
Mag 7, 2019, 1:23 pm

GV, Alphabet Inc’s venture capital arm, led a $58.5 million investment to launch Verve Therapeutics, a new biotech focused on developing therapies that edit the human genome to treat heart diseases.

Interesting short Reuters article about research being funded by Google/Alphabet. Aren't they the same folks who are considering putting their employees consciousness on computers? I think their health care plan has an emphasis on longevity for employees.

30reading_fox
Mag 7, 2019, 5:38 pm

>22 justifiedsinner: - just to be clear. He's not under investigation for getting it wrong. He's being prosecuted for failing to get ethical clearance to do the work he did. He's effectively reduced the chance of any gene edit therapy ever saving any lives. Not because it doesn't work, all science and all medicine go through trials which involve failure and lack of understanding (cf thalidomide) but because he's reduced the chances of patients coming forward (voluntarily having had the risks properly explained to them) and increased the bureaucratic oversight of such trials. He lied to his patients and to his employer.

31justifiedsinner
Mag 8, 2019, 8:57 am

>30 reading_fox: I did not mean to imply that he was being prosecuted for failing. Although, this being China, if he had succeeded wildly would his lack of ethics been penalized?

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