

A Prion Love Story - irollboozers
http://www.newyorker.com/online/blogs/books/2013/09/a-prion-love-story.html

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alexholehouse
My PhD is focussing on addressing fundamental questions in _how_ prions behave
like they do.

Often in medicine edge cases provide insight into a more general mechanism or
process (e.g. Li Fraumeni and p53/cancer, retinoblastoma and Rb). Part of my
work is considering the idea that prion diseases may be very pure examples of
a more general process observed in a huge range of neurological diseases, from
ALS to Alzheimers to Huntington's to Parkinsons.

While there is some fantastic work going on at the clinical/ _in vitro_ side,
I hope that a more general understanding of the physical processes governing
phenotype will help provide a broader class of treatments.

WRT Eric and Sonia's passion for the research - I've done research in a range
of areas, and I've never found a puzzle as fascinating and as engaging as
this. I keeps me up at night. I go through flashes of theories and ideas that
I have notebooks full with possible hypotheses and associated experiments. The
putative overlap in related and unrelated areas of research, from oxidative
damage to epigenetic regulation to arguments relating to 3D diffusion within
the cellular environment, is extensive and both a source of inspiration and
trepidation. Basically, I can entirely relate to that constant feeling of
engagement and interest. My work has accidentally become my hobby, and it's
awesome.

~~~
dnautics
I hate to be a negative nancy, but for most of these diseases I'm not
convinced the answers are in the biophysical properties of amyloids. I still
hold out that biophysics might hold answers for the PrP diseases - mad cow;
kuru; FFI, the subject of the OP - but for most of these other conditions
(alzheimer's, diabetes, Gelsolin Amyloidosis - not parkinsons, which is,
contrary to common grantwriting trends, is not an amyloid), I'm increasingly
convinced that amyloid is not, in the general case, causal, because amyloid is
a general protein fold. There's amyloids that are not cell-malfunction-related
and probably functional (in melanosomes[0], secretory granules[1], and which
bacteria use to grow their extracellular matrices[2]), there's amyloids that
aren't toxic except for causing physical disruption (beta-2 microglobulin
blocks kidney nephrofunction), and there's amyloids which are just garbage
binned proteins (bacterial inclusion bodies[3]). Probably in the ur-times,
early proteins, which were likely overwhelmingly hydrophobic[4] aggregated as
amyloids as an easy, thermodynamically favorable, self-assembling
superstructure, that is regulateable merely by producing to concentrations
above the critical concentration.

[0] Fowler, et al, PLOSBio 2005, the data are terrible - long story, but I
basically redid the experiments and got cleaner, sensical results - but the
conclusion is probably true. [1] Maji, et al, Science 2009 [2] Cherny, et al,
JMB 2005 [3] Wang, et al, PLOSBio 2008 [4] Mannige, et al, PLOSCompBio 2012

I have more detailed reasons to believe the things that I do, if you'd like to
hear more, feel free to contact me. I especially have some interesting tips on
where to look with PrP (I did a short, unpublished project on it that was
inconclusive, but the ideas are intriguing). Long story short, if you are dead
set on being a biophysicist, and you want to really make a difference, focus
on the PrP diseases, the other ones are, in my highly opinionated opinion, red
herrings. Otherwise, focus on the biology. Also, learn your chemistry well, in
either case. Good luck with your PhD. It's a minefield out there.

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Shinkei
Physician here, great article.

Let me say that on the spectrum of diseases if I rank them from weak to strong
in terms of our ability to defeat them:

Bacteria - Virus - Prion

We are so far from being able to treat prion diseases, it is an entirely
different order of magnitude of difficulty than our ability to treat viruses.

~~~
jaggederest
Where do fungi and parasites fall on that spectrum?

~~~
jacquesm
For the most part before bacteria.

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diziet
What's really cool is that the two people got funding for their research on
Microryza, a YC company: [https://www.microryza.com/projects/can-
anle138b-delay-the-on...](https://www.microryza.com/projects/can-
anle138b-delay-the-onset-of-genetic-prion-disease)

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dnautics
these diseases are terrifying, I used to work on the biophysics of diabetes,
which has similar properties at the molecular level - and in our lab we had
people working on alzheimer's and prion biophysics... After a long time, I'm
not sure we know enough to have glimpses of where to begin, besides the
obvious (currently, non-solution of) gene therapy.

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ballard
[http://www.ted.com/talks/russell_foster_why_do_we_sleep.html](http://www.ted.com/talks/russell_foster_why_do_we_sleep.html)

I hope they get a chance to speak at TED themselves.

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shiven
With no intention of trivializing a genuinely inspiring story ...

    
    
       [Deckard picks up paper unicorn.]
       Gaff's voice:	It's too bad she won't live. But then again, who does?
       Deckard :	Gaff had been there, and let her live. Four years, he figured. 
       He was wrong. Tyrell had told me Rachael was special: no termination date.
       I didn't know how long we had together. Who does?
    

Hope in the face of utter uncertainty. Now that's fortitude!

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prjt
For those who are interested and able, a link to donate:
[http://www.prionalliance.org/donate/](http://www.prionalliance.org/donate/)

(I am not affiliated)

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qrybam
Inspiring. I wish them both the best of luck.

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gtani
bookmarked for later read. One of my neighbors worked in Charlie Prusiner's
lab as a postdoc (I lived a couple blocks from UCSF), and i remember being
baffled by how she described her research and thinking I should do some
remedial reading.

