Designer Probiotics. Anyone interested in this?

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naiverahim

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Feb 28, 2012, 12:11:24 PM2/28/12
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Recently I've been really interested in the idea of designing 'good
bacteria' to do even more good for the gut. I've conceived of a way to
design Bifidobacteria (with 2 genes --> 2 enzymes) to destroy fat
before it's absorbed into the body or excreted in feces. This would be
a really cool designer probiotics that would benefit so many people,
particularly those on high fat diets (obesity). Taking Bifidobacteria
longum as a supplement has been shown to resist diet-induced obesity
and mitigate metabolic syndrome in rodents but of course the effects
are marginal. My goal is to shift metabolism towards fat degradation
in these designer probiotics to deliver appreciable benefits. It'd be
nice to have someone to bounce ideas with. Let me know if your
interested so I can send you some good literature on this.

I'll be doing much of the work between City College and GenSpace in
Brooklyn. Anyone in the area?

Bam!,
Rahim

Bryan Bishop

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Feb 28, 2012, 12:52:55 PM2/28/12
to diy...@googlegroups.com, naiverahim
On Tue, Feb 28, 2012 at 11:11 AM, naiverahim <rahim...@gmail.com> wrote:
nice to have someone to bounce ideas with. Let me know if your
interested so I can send you some good literature on this.

Why not send everyone the literature?

thanks,
- Bryan
http://heybryan.org/
1 512 203 0507

Mega

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Feb 28, 2012, 12:53:24 PM2/28/12
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But one problem:

Children in Africa are starving.

And we put bacteria in our stomach to keep eating as much as possible.
If we just ate the half, we had to produce less. Use less fertilizer
(that releases nitrous oxides into the atmosphere! phosphorus reserves
are on the decline,... transport of the food costs fuel -> greenhouse
gasses ,,.... )


And you'd engineer humans so that they couldn't survivie in the
wilderness. In the unlikely case that the whole civilisation crashes,
humans that needed at least 3500kcal would not survive while 'natural'
human with a need of 1500-2000 rather would survive.


I think by that you're creating far more problems than you solve.

naiverahim

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Feb 28, 2012, 1:51:29 PM2/28/12
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or maybe I want to do this so i can help my little brother, mory, who
is predisposed to obesity and diabetes, both of which he and his
mother already have. he hardly eats (eats less than anyone in the
family but gains more weight than most). i want to help people like
mory and that's what i'm going to try to do. and yes i do know about
the starving children in africa and around the world; i was once a
starving child without parents or a permanent home in africa some 18
years ago. i thank god for where I am today. needless to say to me,
but you have valid points and I hope you are doing whatever's within
your means to help these starving kids you took the time to make a
point about. SN: never judge what you don't understand, instead ask
and listen.

in any case, i'm at work now but I will send links to a few relevant
papers on probiotics for management of obesity/metabolic syndrome and
hopefully someone will be interested and join in on the project.

Rahim

Nathan McCorkle

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Feb 28, 2012, 2:32:56 PM2/28/12
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On Tue, Feb 28, 2012 at 1:51 PM, naiverahim <rahim...@gmail.com> wrote:
> or maybe I want to do this so i can help my little brother, mory, who
> is predisposed to obesity and diabetes, both of which he and his
> mother already have. he hardly eats (eats less than anyone in the
> family but gains more weight than most).

Is getting fat really a problem? Or does that mean that your brother
in fact processes food /more/ efficiently than others, and that we
should be looking to people like this to clue us in on how to solve
hunger issues?

--
Nathan McCorkle
Rochester Institute of Technology
College of Science, Biotechnology/Bioinformatics

Nathan McCorkle

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Feb 28, 2012, 2:35:09 PM2/28/12
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On Tue, Feb 28, 2012 at 12:11 PM, naiverahim <rahim...@gmail.com> wrote:
> Recently I've been really interested in the idea of designing 'good
> bacteria' to do even more good for the gut. I've conceived of a way to
> design Bifidobacteria (with 2 genes --> 2 enzymes) to destroy fat
> before it's absorbed into the body or excreted in feces. This would be

By destroy do you mean 'turn to CO2 and heat', or turn into
non-fat/simpler carbon compounds.... non-fat may be more easily
absorbed by the body, which can
then just jump into fatty acid synthesis (consuming simple carbon
compounds are more likely to make you 'fat', than consuming fats)

naiverahim

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Feb 28, 2012, 3:27:12 PM2/28/12
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@Nathan needless to say, fat -> obesity -> metabolism syndrom/diabetes
(problem).
you mentioned studying obesity to fight hunger? that's an interesting
and probably more noble approach worth exploring but the aim here is
to 'destroy' fat.
by 'destroy' fat I mean accelerating beta-oxidation of fatty acids;
this is my hypothesis however the other possible outcomes could be:
(1) nothing or (2) fat-to-carbs conversion (may or may not be
favorable as you've mentioned).

in the case of human liver cells, expressing these two enzymes
resulted in a metabolic shift towards fatty acid degradation (and
releasing CO2). however, i am not sure what the outcome will be when
expressing the enzymes in human gut bacteria, which are under the
anaerobic conditions of the gut (we can clone the enzymes from
pathogenic bacteria such as salmonella, which are stable and
functional in the harsh gastric juices). liver cell vs. gut microbe;
completely different systems but who knows what the phenotype will be.
we'll find out.

rahim

On Feb 28, 2:35 pm, Nathan McCorkle <nmz...@gmail.com> wrote:

Nathan McCorkle

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Feb 28, 2012, 4:03:25 PM2/28/12
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On Tue, Feb 28, 2012 at 3:27 PM, naiverahim <rahim...@gmail.com> wrote:
> @Nathan needless to say, fat -> obesity -> metabolism syndrom/diabetes
> (problem).
> you mentioned studying obesity to fight hunger? that's an interesting
> and probably more noble approach worth exploring but the aim here is
> to 'destroy' fat.

I'm sorry if I misunderstand, but are you talking about destroying the
condition of 'being fat' or the chemicals known as 'fat'?

As far as I know, eating fat produces ketone bodies, whereas eating
sugar and carbs spike insulin which triggers fat synthesis. Destroying
'fat' chemicals in the gut doesn't sound as effective as destroying
sugars and carbs.

Daniel C.

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Feb 28, 2012, 6:07:39 PM2/28/12
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On Tue, Feb 28, 2012 at 12:53 PM, Mega <masters...@gmail.com> wrote:
> But one problem:
>
> Children in Africa are starving.

Is this really a valid criticism? It could potentially be applied to
any human activity that isn't related to feeding starving African
children... and yet I still do my homework, go to work, and eat a
little bit more than I strictly need to and nobody seems to be getting
morally indignant about it.

-Dan

Jeswin

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Feb 28, 2012, 9:09:01 PM2/28/12
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On Tue, Feb 28, 2012 at 4:03 PM, Nathan McCorkle <nmz...@gmail.com> wrote:
>
> As far as I know, eating fat produces ketone bodies, whereas eating
> sugar and carbs spike insulin which triggers fat synthesis. Destroying
> 'fat' chemicals in the gut doesn't sound as effective as destroying
> sugars and carbs.
>
> --
I was going to point to this. Some decades ago, scientists made fats
the boogie-man. Looking through the cycles in our body, it seems that
sugar is the main culprit. And while fat intake may have been reduced
over the years, sugar intake has gone up. Sorry that I can't give any
resources. Maybe someone else can support what I'm saying with some
references?

romie

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Feb 29, 2012, 2:16:46 AM2/29/12
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I'm really interested in the idea of modified got bacteria. I don't
really care about the obesity issue compared to overall health but I
think the problems of integrating something new into such a complex
environment is a shared problem. I'm not in your area but can pursue
this idea at LA biohackers.

Romie

Cathal Garvey

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Feb 29, 2012, 3:58:20 AM2/29/12
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To address sugar, try knocking down sucrase expression, perhaps using modified plant miRNAs, and give yourself an upper tract probiotic that produces levansucrase. Undigested sucrose is probably poorly digested, and the conversion of sucrose to levan (a prebiotic/gut conditioner) turns a poison into a mild beneficial compound.

Alternatively, omit the levansucrase part: cramping and diarrhea from undigested sucrose will teach you to stop drinking coke in the first place.

romie <ryro...@gmail.com> wrote:

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Nathan McCorkle

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Feb 29, 2012, 4:19:40 AM2/29/12
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On Wed, Feb 29, 2012 at 3:58 AM, Cathal Garvey <cathal...@gmail.com> wrote:
> To address sugar, try knocking down sucrase expression, perhaps using modified plant miRNAs, and give yourself an upper tract probiotic that produces levansucrase. Undigested sucrose is probably poorly digested, and the conversion of sucrose to levan (a prebiotic/gut conditioner) turns a poison into a mild beneficial compound.
>
> Alternatively, omit the levansucrase part: cramping and diarrhea from undigested sucrose will teach you to stop drinking coke in the first place.

Re: coke and sucrose content:
It says here (on page 205, in case the link doesn't load right), that
sucrose has a tendency to invert (sucrose -> glucose + fructose) quite
a bit at room-temp (a few temp curves presented):
http://books.google.com/books?id=EiD7ZPwIIEcC&pg=PA205#v=onepage&q&f=false

Douglas Treadwell

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Feb 29, 2012, 5:05:00 AM2/29/12
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Seriously, should we throw away all our electronics, modern medicine, sanitation, nice housing, electricity, etc. and sacrifice everything at the altar of poor starving children in Africa?  It seems to me that more and faster progress will lead us to the solution faster than reducing our use of the advantages progress has brought us.  Reduce obesity, we increase healthy lifespan of people in the first world.  Some of these people are highly educated and may be contributing to the scientific progress that will lead to people in Africa having the same first world amenities.  Personally I think our goal should be to achieve a post-scarcity society as soon as possible.

CodonAUG

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Feb 29, 2012, 9:46:38 AM2/29/12
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I am a bit wary of probiotic hype. But science based medicine does a
better job than I do in explaining.
http://www.sciencebasedmedicine.org/index.php/probiotics/

naiverahim

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Feb 29, 2012, 11:00:17 AM2/29/12
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@ Nathan, here i am talking about destroying fatty acids (chemical).
Here is a decent paper studying the effect of reduced fat diet on body
weight and glucose tolerance; its a long-term study.

http://care.diabetesjournals.org/content/24/4/619.long

I understand that carbs are a better target but I have not yet
conceived of a way to dealing with carbs (although i will look into
the suggestions made in this thread). Feel free to join the effort.

On Feb 28, 4:03 pm, Nathan McCorkle <nmz...@gmail.com> wrote:

naiverahim

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Feb 29, 2012, 11:02:53 AM2/29/12
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@romie, awesome. i am too more generally interested in the overall
health. probiotic applications in obesity is just my current project
of interest. lets talk off-line. i'll email you.

naiverahim

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Feb 29, 2012, 11:19:48 AM2/29/12
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@codonAUG Dr. Crislip, the author of the article, seems to be in the
business of skeptical criticisms of science and probably has something
to say about everything in medicine. as with any therapeutic
approaches, he makes some valid point regarding the safety and
potential risks associated with probiotics and the lack of scientific
evidence supporting some of the health claims made by those who are in
the business of manufacturing and selling probiotics, which are hardly
regualted if marketed as dietary supplements.

but what i think he fails to admit, unsurprisingly, is the potential
benefits of probiotics if studied and engineered adequately to deliver
health benefits with reduced short- and long-term side effects. this
is why we do science to enable ultimately such capacities. the gut is
a complex system that is largely responsible for regulating what goes
into our bloodstream/body. the ability to engineer this system to
afford health benefits has a broad application in health and medicine
and can potentially lead to management of a host of health problems.

rahim

Zebedeeboy

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Feb 29, 2012, 1:20:43 PM2/29/12
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Hmm,

Knocking out sucrase will leave lots of undigested sucrose in your GI tract and give you a nice osmotic diaorrhea. Not going to do much for the sales of Coke (unles it's Diet). You will lose weight though :-)

Zeb


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-------- Original message --------
Subject: Re: [DIYbio] Re: Designer Probiotics. Anyone interested in this?
From: Cathal Garvey <cathal...@gmail.com>
To: diy...@googlegroups.com
CC:


To address sugar, try knocking down sucrase expression, perhaps using modified plant miRNAs, and give yourself an upper tract probiotic that produces levansucrase. Undigested sucrose is probably poorly digested, and the conversion of sucrose to levan (a prebiotic/gut conditioner) turns a poison into a mild beneficial compound.

Alternatively, omit the levansucrase part: cramping and diarrhea from undigested sucrose will teach you to stop drinking coke in the first place.

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CodonAUG

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Mar 1, 2012, 9:22:53 AM3/1/12
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There is no 'business of skeptical criticisms of science' because
skeptical criticism is the the norm for science.

Richard Proctor

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Mar 1, 2012, 10:09:33 AM3/1/12
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I doubt that the side effects of diaorrhea would be a problem with
people using this potential probiotic so long as they are made aware
of it.

lets not forget that one of the most widly used obeesity medications
orlistat comes with the side effect of squits if you eat to much fat.
Infact they have made it a selling point of providing an " adversion
therapy."

I think it is absolutely necceseary to build in some kind of adversion
into an anti obesity treatment. You don't want to send the message
that " woohay science lets you eat as much crap as you like and never
get fat." All that will lead to is an increse in US levels of
consumption.
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