
New universe of miniproteins is upending cell biology and genetics - furcyd
https://www.sciencemag.org/news/2019/10/new-universe-miniproteins-upending-cell-biology-and-genetics?rss=1
======
ccvannorman
* _' Small proteins also promise to revise the current understanding of the genome. Many appear to be encoded in stretches of DNA—and RNA—that were not thought to help build proteins of any sort. Some researchers speculate that the short stretches of DNA could be newborn genes, on their way to evolving into larger genes that make full-size proteins. Thanks in part to small proteins, "We need to rethink what genes are," says microbiologist and molecular biologist Gisela Storz of the National Institute of Child Health and Human Development in Bethesda, Maryland.'_

Wow. Amazing how incredible biology and proteins are and their still-barely-
understood mechanisms. For anyone who hasn't already seen it, I highly
recommend The Inner Life of a Cell [0]

[0]
[https://www.youtube.com/watch?v=wJyUtbn0O5Y](https://www.youtube.com/watch?v=wJyUtbn0O5Y)

~~~
Dev_2019
We aren't curing aging any time soon are we :(?

~~~
jerf
I wouldn't be surprised in the slightest that it is easier to build a brain
scanning machine and simulate you in a computer than to "solve aging".

And don't think I underestimate the difficulty of that, either.

~~~
sasaf5
Making a very crude analysis based on the size of data, I would say solving
aging is a piece of cake comparing to scanning someone's brain content. Our
proteins that eventually break down with aging are coded by the DNA. The DNA
is a few GB across. Sure there are mutations, folding and other complexities,
but it is still mostly digital data. The brain has 80B neurons, each with
thousands of dendrites. You'd need to scan not only the (real valued) state of
the neurotransmitters in each of these dendrites, but also the topology of the
(varying) connection to other neurons. Not that it isn't a daunting challege,
but I would bet my money on beating aging, rather than scanning the brain.

~~~
jerf
It depends on how close the biological cells are to being immortal. What I was
referring to in somewhat sarcastically in another post is that modern
senescence research is basically operating from the position that the cell
just has, you know, maybe one or two or three things wrong with it, and if we
can "just" extend the teleomeres (presumably with just ingesting some
substance), and maybe supplement our diet with a couple of substances, and
maybe fix cancer or something, we'll be there.

There are some reasons to believe this may be true, such as the existence of
cells in the wild that seem to be effectively immortal, like certain jellyfish
and such. (Nothing terrible close to us taxonomically, but at least they're
from planet Earth.)

On the other hand, it may turn out that after a couple of quick wins worth,
say, 20 or 30 years, that the whole thing devolves into dozens, then hundreds,
then thousands, then tens of thousands of interventions, all complicating each
other, a good number of them unique to the individual, as you try to pick up
the pieces in your ever-aging organs as they continue to find new and exciting
ways to fail. Imagine trying to keep an old car running, but you're not
actually allowed to just replace parts, and you have to do all the fixes while
the car is on the road, and this is just barely the tip of the iceberg.
Senescence research may be one of the worst examples of a light-post problem
in human history, as they search for this or that substance that will fix
aging but the minimal solution is in fact literally gigabytes worth of
information converted into biological machines we can barely even conceive of.

If you can read one neuron, you can read two; those problems are not
independent. (That's a simplification to some extent, but at this level we'll
take it.) If you can understand one protein's function, that doesn't help
anywhere near as much with the next one, and the state of the body is roaming
through a very high-dimensional space over time, with the interventions all
also affecting the next intervention that will be necessary... it can get
pretty ugly in there, potentially. Amusingly, the brain is the problem in both
cases; biological immortality probably wouldn't be so hard, we could probably
solve everything by transplants of freshly-grown organs based on our genetic
code... except transplanting a freshly-grown brain in kinda defeats the whole
purpose. In the end, both problems may come back to scanning brains one way or
another.

------
newsocks
How are miniproteins any different than just peptides?

The article references "miniproteins"as being the same as "minipetides"... as
though these are both different from regular peptides.

Wikipedia states that peptides are "approximately 50 or fewer amino acids" [0]
while minipeptides are "a length of less than 100-150 amino acids" [1].

Is this article really just saying that "peptides are upending cell biology"?

[0]
[https://en.wikipedia.org/wiki/Peptide](https://en.wikipedia.org/wiki/Peptide)
[1]
[https://en.wikipedia.org/wiki/Micropeptide](https://en.wikipedia.org/wiki/Micropeptide)

~~~
gilleain
The boundary between 'peptide' and 'protein' is a little fuzzy. There are
'small proteins' like:

[https://en.m.wikipedia.org/wiki/Thionin](https://en.m.wikipedia.org/wiki/Thionin)

that are 45-48 amino acids which is less than the (arbitrary) lower limit of
50.

One distinguishing feature of a protein is that it folds, while peptides
usually are too short to have a defined fold.

~~~
glenvdb
> while peptides usually are too short to have a defined fold.

That's not strictly true. My PhD project has looked at an entire class of
peptides that are known to fold in to alpha-helices when bound to a cell
membrane e.g.
[https://www.rcsb.org/structure/2k9b](https://www.rcsb.org/structure/2k9b).

There are many others that are known to fold into beta-sheets too.

~~~
gilleain
Fair, but I would not really call a single helix a 'fold', either!

Ok, so I'm playing with definitions here a bit. Clearly 2k9b adopts a helical
structure so it is 'folded' in some sense. However it has no tertiary
structure.

Structural proteins like collagen are different again. They have a simple fold
that could be described as quaternary (multichain), although that is again an
abuse of terminology.

There are also some small proteins (peptides?) held together by disulphide
links that have no secondary strucure to speak of. I think these are Class 4
in CATH, but I do not remember.

What is an example of a beta-sheet peptide? Amyloid is beta, I thought, but
sheets are not normally stable outside sandwiches, barrels, etc

~~~
flobosg
> What is an example of a beta-sheet peptide?

WW domains[1] fold stably into a three-stranded sheet. Also, not strictly a
sheet, but beta hairpin motifs (e.g. tryptophan zippers[2]) are known to be
stable isolated from their parental domains.

[1]: [http://www.rcsb.org/structure/5VTJ](http://www.rcsb.org/structure/5VTJ)

[2]: [http://www.rcsb.org/structure/1LE0](http://www.rcsb.org/structure/1LE0)

------
abledon
""" _Later in life, myoregulin steps in to help regulate muscle activity. When
a muscle receives a stimulus, cellular storage depots spill calcium,
triggering the fibers to contract and generate force. An ion pump called SERCA
then starts to return the calcium to storage, allowing the muscle fibers to
relax. Myoregulin binds to and inhibits SERCA, Olson 's team found. The effect
limits how often a mouse's muscles can contract—perhaps ensuring that the
animal has muscle power in reserve for an emergency, such as escaping a
predator. Another small protein, DWORF, has the opposite effect, unleashing
SERCA and enabling the muscle to contract repeatedly._ """

I've noticed when I take magnesium that my muscles really relax, and jaw
doesnt tighten as much when I sleep. this is from what i understand, because
Magnesium acts as a natural calcium blocker, helping your muscle cells relax
after contracting preventing excess muscle contraction (tightness). An
interesting avenue i've started exploring is attacking the problem from
another angle and instead of using mg, lying on a grounding mat plugged into a
wall, which after reading this, is providing extra grounding for the "ion
pump" described above? After sleeping on that mat, i feel even more relaxed
than downing 500mg of magensium, i can even feel like the inner heart area be
able to relax, which otherwise felt uncommandable to relax.

Ben greenfield, a biohacker whos pumped his entire body full of stemcells at
one point (including the netherregions), has recently been investing it [1]

I can imagine since we know _so little_ about how even proteins and now these
mini proteins work... how is the underlying electric system affecting the
whole interaction a couple of abstraction levels up!?! what happens when the
entire system is operating under a slight electric potential for 80% of
lifetime, as opposed to being grounded? (static in a television signal)

[1] [https://bengreenfieldfitness.com/podcast/biohacking-
podcasts...](https://bengreenfieldfitness.com/podcast/biohacking-
podcasts/earthing/)

------
Jaygles
Imagine trying to understand biology like we try to understand what we code
day to day. I would need a brain at least 100x as large and efficient.

~~~
hprotagonist
This is "the andy grove fallacy": it's not clear that you actually _can_ ,
because code and computational hardware was designed by humans and biology
emphatically was not.

[http://blogs.sciencemag.org/pipeline/archives/2007/11/06/and...](http://blogs.sciencemag.org/pipeline/archives/2007/11/06/andy_grove_rich_famous_smart_and_wrong)

~~~
tolstoshev
I'm starting to wonder if there are physical limits to cognition and if we've
already hit them. Maybe it's impossible for the physical universe to
understand its own complexity.

~~~
hoseja
We've hit them long ago. We're now using massive parallelization to go
forward.

------
GenerocUsername
I have a 4 year degree in "Biology" and all I learned was that life does a
little bit of everything everywhere.

There are patterns which we classify, but there are rule breakers at every
turn because our classifications are not truth

~~~
nydev
This is my understanding too. Evolution didn't work of a master plan with
clear divisions between systems..just whatever happened to work at the time.

------
AlexCoventry
Seems a bit sensationalistic -- proteins with only a few dozen residues have
been known for decades. What's the new development, exactly?

------
RosanaAnaDana
Oof. Every year I regret not sticking with genomics/ biology. Its changed so
quickly that even what I learned at the beginning of this decade seems very
outdated.

------
bigmit37
I love these discoveries. Are proteins easy to detect and isolate? How does
one tell where a protein begins and ends and if one megs protein is not just a
bunch of smaller proteins.

Also how do they discover the functions of proteins? Just turn them off and on
and try to see what effect it has on the body?

This is such a super interesting field; Any one have good resources (youtube)
that show how this stuff is done in the lab?

------
cwkoss
Disclaimer: These are novel chemicals and most sources you can find them from
are questionable at best. Don't even consider using these without deeply
researching the risks from the specific peptide, the quality control of the
supplier, as well as the inherent risks of injecting substances of
questionable purity.

\---

BPC-157 is a really interesting peptide

[https://en.wikipedia.org/wiki/BPC-157](https://en.wikipedia.org/wiki/BPC-157)

"It has been tested in animal trials for cytoprotective and wound healing
activities. BPC-157 can contribute to wound healing due to muscle and tendon
rejuvenating properties through accelerating the rate of angiogenic repair."

It is cheap and readily available (on Amazon even!), when injected it appears
to greatly accelerate recovery from injuries - it's been called the "Wolverine
drug" (as in the x-men character with superhuman healing powers). It requires
injection, so its use is most common in bodybuilders who are aren't as averse
to injecting questionable substances.

Many stories from people claiming it successfully repaired years-old tendon
injuries and such. Some claim that oral administration can help with gut
issues as well.

Some select testimonials: Rotator cuff injury recovery -
[https://www.reddit.com/r/Peptides/comments/8iqbv9/bpc_157_is...](https://www.reddit.com/r/Peptides/comments/8iqbv9/bpc_157_is_living_up_to_the_hype/)

Bicep tendon rupture recovery -
[https://www.reddit.com/r/powerlifting/comments/5ewi2j/bpc157...](https://www.reddit.com/r/powerlifting/comments/5ewi2j/bpc157_for_tendon_repair/)

Non-surgical repair of rat achilles tendon -
[https://www.ncbi.nlm.nih.gov/pubmed/16583442](https://www.ncbi.nlm.nih.gov/pubmed/16583442)

\---

Melanotan is another interesting one - it's an injectable peptide that
increases melanin in the skin. From the image journals I've seen reporting
progress over time, it definitely is highly effective - one individual used
for several months and went from a pasty caucasian to looking Indian or almost
Black. He decided to discontinue his trial when his friends started making
'blackface' comments.

\---

I think it's a really exciting area of research, and I'm glad the people
willing to take these risks post about it so readily on the /r/Peptides
subreddit. Not for me, but I'm glad they're publishing the results of their
n=1 studies!

~~~
Balgair
Melatonin and Melanin are closely related chemicals that are used all over the
body and are synthesized in the body through related mechanisms and pathways.
Melatonin is used in the sleep-wake cycle and melanin is used by the skin to
darken it and protect from solar radiation. When you need to sleep and when
you need solar protection tend to be inversely related. The interaction
between these processes is still being studied and is likely to involve many
other things currently not under study.

In general, unless you are under the close supervision of your doctor, I would
HIGHLY AVOID injecting peptides or really any other thing into you. In
relation to just melanin and melatonin, the interactions are complicated and
not well understood. We likely do not have the full picture of what melanin is
doing in your body and there could be big problems. There also could be no
problems at all. That said, I would not want to be the test cases for a M&M
conference on this.

I do not think that people on /r/peptides are doing anything but unnecessarily
putting their health at risk and (possibly) doing harm to their families,
friends, and other relationships. As we know so little about this area of
research, the risks are not well constrained and could result in death or
worse. When it comes to health and wellness, especially biochemically, it is
much better to leave it to ethical and well trained medical researchers that
know what to look out for and how to help when things go bad. Auto-biochem
hacking is a hard pass from me for now.

~~~
meesles
While I agree personally, I am comfortable letting others experiment with new
drugs and take on that risk with the potential to discover things a bit faster
than traditional medicine. Regardless of what you think of CBD, it has
garnered steam because of non-medical use and I think brought it up to popular
culture which researchers are then hearing about and interested in researching
more.

At the end of the day, in the USA, we tend to avoid telling adults what to put
in their bodies. I like it that way and I see this as just an extension of the
same thing.

That being said, they shouldn't be selling their solutions or misleading
people with non-existent medical data. You are hacking your biology, death and
injury are very real potential risks you can only accept for yourself.

~~~
dekhn
researchers have been working on CBD much longer than it was in the popular
culture (I'm not contradicting your statement that it garnered steam in the
popular culture). For example, in England there is a whole company that has
gotten CBD through clinical trials and approval (you couldn't have done this
in the US at the time). The researchers knew two decades ago that CBD had
medical potential, although they only completed trials in 2015 and it was
approved in the US in 2018.

One of the big changes for researchers (in the US) is that it's a lot easier
to obtain materials, but it's still really onerous.

------
jeffml84
How long before pharmaceutial companies tell you that you have a "miniprotein
imbalance"

------
hinkley
In retrospect it’s shocking that we are surprised by this.

When life evolved on earth wouldn’t it have first been dominated by shorter,
less complex proteins? Why assume all of those have disappeared? Especially
when we have some pretty archaic forms of life still around?

------
aiphex
Super interesting. On a side note the disappearing / reappearing top bar on
the science site is incredibly annoying.

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gateKeeper
That was the most interesting article I have read in a while. Thank you for
sharing.

