Research for Prions

[deleted-145489]

Hi,

I sent a post earlier asking about prion research, but I am not sure if it went through, so I just want to repost it here.

I am a high school student in 11th Grade looking to enter the Science Fair in March 2014, and the topic that I want
to look more into is prions and their effects on the human or vertebrae brain, as well as possible
prevention options. I was wondering, do I need to do animal testing? Where can I get prions?
Do I need to use disabled prions?

Thank you!

[SciB]

Hi bb87,

You have chosen a very interesting and exciting research area but one that is not going to be very easy to experiment with. If you live near a university where there is someone doing research on prions, you could approach them as a student volunteer to do a project in their lab. Prions can cause human diseases such as Kreutzfeldt-Jakob and these abnormal proteins are transmissible, so they are dangerous to work with. They have to be handled under Biosafety Level 2 conditions at a minimum and many labs use BSL3 procedures, which would be way beyond a high school’s budget. Also, the ISEF rules prohibit experiments on BSL3 agents (https://www.sciencebuddies.org/science- ... ents.shtml).

So, if you want to pursue a study of prions, which I think you should since you are really interested in them--my suggestion would be to make your project a virtual one. This will require a fair amount of reading and searching the literature on prions to come up with a hypothesis that can be tested using available online data and software, but it is doable. Prions and their targets in humans have specific amino acid sequences and secondary structure, and there are molecular biology programs into which you can put an amino acid sequence and obtain data about the form of the protein (http://en.wikipedia.org/wiki/List_of_pr ... n_software).

I have read that there is some relation between the abnormal protein in Alzheimer’s disease, beta amyloid, and the way prions do damage to other brain proteins. Maybe you could work the two into a hypothesis and then test it by looking at structure virtually and seeing how changes in amino acid sequence might affect their interaction, folding and deposition in the brain.

Think about where you want to go with your prion project and get back with us and I will continue to help you. Good ideas can come from anyone and you may hit upon something to test that other scientists have overlooked because they all tend to think along the same lines.

Best wishes,

Scibee

[deleted-145489]

Hi SciB,

Thank you so much for your detailed and prompt reply! I am truly grateful for the project idea that
you have given me, and did not even think that I could take this project into a virtual direction,
which seems much more feasible than what I had originally thought of. I will discuss this with
my teacher tomorrow and see how I can build off of your suggestions.

I was also just curious, where have you read about the correlation between Alzheimer's disease and
prions damaging the brain proteins? That sounds like something I would definitely be
interested in further researching, and was wondering if you read this in a science journal
or other literary source, so I could start from there to begin my task.

Once again, thank you so much and I will not hesitate to contact you once I know more
about my intended project direction and if I come across any difficulties.

[SciB]

You are welcome! I'm happy to help get you going. I think this idea of an abnormal protein that can make humans sick and even kill them just by causing misfolding of normal proteins is a really scary thing!Scientists need to definitely do more research on them.

I looked up prions and Alzheimer's on PubMed and got over 450 papers, so there is a lot of interest in this. I have attached the review that I read where the idea of Alzheimer's being similar to prion disease is discussed [Soto et al.]. I also found a review that i had not seen published in July 2013 where the author says maybe prions CAN actually be transmitted by bacteria. After all, a prion is just a whacky protein and bacteria make all kinds of proteins.

Virtual projects can be really important to understanding science. Many times scientists are so busy with writing grants and papers, going to meetings, supervising grad students, etc. that they don't have time to look at the data that has been published and manipulate it using the molecular biology programs available free [usually] online.

The sequence of the PrP has been known for years but I have never heard of anyone suggesting that certain microbes might carry prions. There is a program called BLAST [http://blast.ncbi.nlm.nih.gov/Blast.cgi ... =BlastHome] that allows you to look for a particular sequence in a protein database of a group of organisms. That might be a place for you to start. It takes a little work to learn the software but it is worth the trouble. All scientists use these programs a lot.

I'm glad you are going to study this question and maybe you will discover something nobody else has seen. That's the exciting part of science--being the first to find out something new. Keep posting on this thread and we'll be here to steer you on your way.

Best wishes,

Scibee

[SciB]

BB87,

Here's the second review. I can only attach one item at a time.

Scibee

[deleted-145489]

Thank you so much once again!

I am looking into those links. I have worked with BLAST before but didn't realize that it can totally help out here!
I will also look more into PubMed to discover more scientific papers. It would be really cool to discover something
never before seen.

Thank you once again, and I will continue to post here if I need anything else! It looks like
I have lots to work with and get my project going.

[deleted-145489]

Hi,

I was looking more into the connection between prions
and Alzheimer's disease, and unfortunately there is already a plethora
of information on this topic, so I decided to slightly change my topic
to trying to change the structure of an infectious form of the prion
into the noninfectious (normal) form by using protein modeling software
and proposing several models using this software.

However, I have no idea how to use protein modeling software and
which ones are good, bad, useful for me, etc.

Is there anyway that I can find out more information about which
products are good, or even help using one? I tried Googling
but I ended up really confused on what I was finding
because there are so many and I have no experience
in computer science.

Thank you so much!

[deleted-140078]

Protein folding software is quite complex, and the more advanced systems actually require the rental of server space. There is an obscene amount of calculations that go into it. I have not looked at software, so I will try to do some digging for you and see if there is a good source. In the mean time I will shoot an e-mail off to an old professor of mine and see if he has any input.

The other thing to consider is how to adjust the structure or denature the protein. Heat, chemicals, etc can change protein shape. It may be worth looking into ways to damage the pathogenic protein while minimizing damage to the hosts proteins.

[deleted-145489]

Thank you for your prompt reply!
I look forward to hearing from you soon.

For damaging the pathogenic protein,
can that be done virtually, or does that have to be
done manually? I do not believe that I can actually access
prions because they are at such a high biosafety hazard,
but if there is a way to do this virtually I am all for learning
how I can this.

Thank you so much for going through such lengths for me again!

[deleted-140078]

The virtual part is going to be up to you really. FInding places in the structure that are less bond dense and therefore easier to manipulate. Doing it in a practical sense would be impossible in your situation for the reason you already stated.

Here are some resources my professor wrote back with. Hope these help.

Here is a site with some references regarding treatment of pathogenic prions. http://www.ncbi.nlm.nih.gov/pubmed/24093082

Another good place to start http://www.ncbi.nlm.nih.gov/pubmed/21679685#


He also replied with the suggestion to use the program Raptor X. Here is a wikipedia link with some descriptions. I however are unfamiliar with this program, but the page gives some decent input.

May I also recommend you reach out to a local university that has a genetics program, or maybe even an infectious disease physician. There is always ongoing research going on at universities that may be related to what your doing.

[deleted-145489]

Thank you so much!

I will try working with Raptor X and see where I can go from there,
as well as try to reach out to a local university in my area to
work with a researcher regarding my project.

Thank you again, and I will post again if I need further help!

[deleted-132180]

Hello there,

You've gotten lots of great advice from all the experts that have posted! I would like to offer one of my suggestions as well. I think that taking your project in a virtual direction is a great idea, considering how human prions are dangerous to work with, but if you are thinking about doing experiments with actual prions, I may suggest perhaps finding a lab that works on yeast prions. Budding yeast has been one of the most popular model organisms used to study eukaryotic cell biology, and recently, prions have been found in yeast and have been used as models to study how prions are formed. The knowledge obtained from these studies could provide important implications about how prions are formed in mammals! Also, I would think that it's probably not as dangerous to work with yeast prions than with actual mammalian prions (although I don't personally work with prions myself, so if anyone has the expertise and sees anything wrong with this comment, please correct me), and budding yeast is a a really easy organism to grow and work with. Attached to this comment is a short review article about yeast prions in case you were interested.

Let us know if you have anymore questions.

Connie

[deleted-145489]

Hi Connie,

Thank you so much for your suggestion! I truly am
grateful for all of the great advice I have been given
on this forum, and I'm sure I would not be where I am
now, almost ready to begin my project, if it wasn't
for this forum. Actually, to refer back to an old suggestion,
I want to use Raptor X but I am so confused on how to use it,
so any suggestions would be very much appreciated! (I haven't
been able to find a "Raptor X for Dummies" unfortunately...)

I have never actually heard of yeast prions before, so I
think I will try to contact a local lab to see if I can get more
experience working with these organisms...they sound really cool!

Thank you again, and I will post again if I need anything else.

[deleted-145489]

Hi,

I was working on my project virtually,
but wanted some advice and where to search
for an amino acid sequence for the prion?
I have tried Googling, and so far have only
found one for mice...

Thanks for all the help I have received so far!

[deleted-140482]

Hi,

You can find sequences to any number of proteins at the NCBI protein database:
http://www.ncbi.nlm.nih.gov/protein/?term=prion
Just search for your protein of interest. Click on the link. Towards the bottom of the page on the protein, you will see an amino acid sequence. This sequence first has a number and then a bunch of letters. The letters are the amino acid sequence (we use a single letter code to represent different amino acids. If you are not already familiar with this code, it should be easy to find online).

Also, although I'm not particularly familiar with Raptor X, you can find a number of different protein structures at the RCSB PDB database: http://www.rcsb.org/pdb/results/results ... ow=Current
Oftentimes different protein modeling programs can open these files, and they often already have the protein sequence embedded in the file.

Hope this helps and good luck!
JMP

[deleted-145489]

Hi JMP,

Thank you so much! I will definitely utilize the resources
you have provided.

[deleted-145489]

Hi,

I have nearly completed my project, thanks to all of
the wonderful resources and suggestions that I have
received on this website- thanks again to everyone who
suggested something because it all really helped!

I will be presenting my research in front of a panel
of judges very soon, and I'm just worried about the
part where they question the presenter for a few
minutes. Does anyone have any suggestions/ prior
experience with what type of questions they could ask?

Thank you again, and I look forward to getting a response
soon!

[SciB]

Hi bb87,

I'm glad to hear you have almost completed your project. Did you discover a way to eliminate a particular prion?

With regards to the judging, the questions usually fall into two categories--(1) the background information about the subject and (2) how you conducted the research. I'm sure they will ask you things like what is a prion, where do they come from, how are they harmful, what are some examples of prion disease [mad-cow, kuru, and others], who discovered them and how can you protect yourself against them.

Your presentation and your poster will answer most of these questions, but just make sure you understand what a prion is and how it is harmful to humans and other animals.

Also, be able to explain what the RaptorX program is, what it does and how you used it. The main thing a judge looks for in a science project is whether your conclusions are supported by the evidence; so be very careful in stating the conclusion.

Don't be afraid to say I don't know. They don't expect you to know everything. Just be sure that what you do say is accurate. Learn the technical terms that are used in prion research and make sure you use them correctly. Practice a couple of times in front of your friends and family and let them ask you questions. Trying to explain something to a non-scientist is a really good way for you to test your own knowledge. You should be able to describe the research in a way that your friends and family can understand.

You are really enthusiastic about this subject and I know you will do fine. If you have any specific questions, let us know and we can try to help you.

Best wishes,

Sybee

[deleted-145489]

Hi,

Thank you for the helpful suggestions! My presentation was today,
and it went well, thanks to these suggestions. I will find out
by next week if I have been selected to move on to finals.

I found a way to eliminate a prion by possibly preventing its formation
by using a certain chemical - I intend to use different software to perhaps
model this chemical and its effects very soon.

I will post if I need any further help! Thanks again for all the help
I have received so far!

[SciB]

Congratulations, GG! We are proud of you. Do let us know the results of the judging. And, if you have any follow-up questions based on what the judges asked you, please post them as these are important for others to know about. Every project you do teaches you some things that you can use in the next project--so, you keep getting better and better!

Keep working with prions. They are really weird little beasts that need to be studied.

Cheers!

Sybee

[deleted-145489]

Hi,

Thank you so much! I will definitely post as soon as I can about
the results for JSHS.

If judges ask you if your project has been completed, you
should probably say "no," right? I truly haven't completely
finished my project, but should you ever say your project
is 100% done?

Prions really are fascinating, but also really scary.

Thanks again for all of the positive encouragement!
It really makes my day!

BB

[SciB]

We are happy to help you, BB! Science is such cool beans we like to spread the word.

If the judges ask if you completed your project i think they mean did you do all the experiments that you planned for the CURRENT study, not for other future studies. Science is never done. They know that. We will always be discovering new stuff that changes what we thought before. That's what makes science so interesting.

And as you say, there are a lot of scary things out there; but i think the best way to manage them is to try and understand them well and the scientific method is the best way to do that.

Hope to work with you on your NEXT project!

All the best,

Sybee

[deleted-132180]

Hi BB,

SciB already gave you some excellent advice, but in addition to those questions that she had already mentioned, I think one very important thing is to show the judges that you're enthusiastic about science and that you're really excited about your project. Also, I think that it's also great if you also think about what future experiments you can possibly do if you want to follow up the work that you did here, and also what kind of real world problems your project could potentially address. Talking about science and sharing your research project with an audience is not just about explaining the logic behind your experimental set up and analyzing your data, but it's also very important to convince your audience why the project you're doing is important and how it can impact real world problems. I think what you mentioned about looking to see if there is a way to eliminate prions chemically is great, and this is so important because prions can cause deadly diseases! It is also great that you already have some ideas in mind about future directions because it shows that you've been thinking about your project extensively and how to take it further in the future.

Sounds like you have a very great project and I'm sure that your presentation will go really well. Do let us know how it goes and if you have anymore questions about anything!

Good luck!
Connie

[deleted-145489]

Hi Connie and SciB,

Thank you for the wonderful advice that you both have contributed! I'm
really grateful to have received this info.

My presentation was pretty successful in my opinion. In my acknowledgements,
I forgot to mention, I did mention "Science Buddies" and the "Ask an Expert"
program because of people like you guys and the other experts that
contributed to helping make my project a success.

I just found out today that I wasn't accepted to move onto the next
round and become a Finalist, and I was very displeased and disappointed,
especially since the judges seemed to have a positive reaction to my project.
However, I'm still proud that I was able to complete a research project
and also utilize the wonderful resources I received here. I'm going
to take what I learned to improve my project and see
if I can be more successful in future competitions.

Thanks for everything!

BB

[SciB]

You are certainly welcome, BB. We are happy that you successfully completed your project and learned a lot.

As a scientist, I am frequently rejected in submitting grant proposals and manuscripts for publication in scientific journals. You learn, as you said, from your mistakes and constantly improve until you succeed. The one most important thing I have found is good planning. Spend the time at the beginning reading the literature and devising good experiments. I have seen the data from a whole series of expensive and time-consuming experiments have to be thrown out because the researcher forgot to include a key control.

Run your ideas and proposals by us and we will be happy to critique them for you and make suggestions for improvement.

All the best,

Sybee

[deleted-145489]

Hi,

Thank you! Actually, this project is not quite finished
yet, so I'll post again if I need further help.

BB

[SciB]

Hi again,

Sure, we will be happy to answer as many questions as you have. What do you think you could have done differently to get a better rating from the judges? Do you think it was because the project was done online and did not involve physical experiments? I'd like to know because feedback like that could help us design better science projects.

Sybee

[deleted-145489]

Hi,

I have not heard back the exact comments that the judges had regarding
my project, but I learned from the program director that the projects
that did end up advancing were ones where students had a personal
connection, like water problems in India. Even the ones where students
got into a high-powered lab were very successful.

Based on this, I think I have an idea for what I want to do next year.
I hope this will be helpful for future students to keep in mind as
they decide their research topics.

Thanks for all the support!

BB

[deleted-132180]

You're welcome, BB. I'm glad to hear that you had a great time presenting your work to the judges. Even if you were unable to advance to the next round, I hope you take this as a good learning experience and as a chance to see how you can improve and be better next time! You were able to conduct your own science project about something you find really interesting and got to share your results with others. Being able to practice talking about your research with a broad audience is a very important part of science. One can make amazing discoveries but all of that would be meaningless if they do not communicate these results to others. It is really great that you have taken advantage of opportunities to learn more about science and research!

Let us know if you have anymore questions.

Best wishes,
Connie

[deleted-145489]

Hi,

I was editing my research paper, and I had a quick question.
I used a particular software in hopes of achieving my goal, but that software
didn't end up working out. Should I still mention it in my paper as one "trial"
that I used to try to answer my research question? Also, how long should a research
paper be? My paper is looking to be around 30 pages or so and it shouldn't go
for much longer, because a ton of space is taken up by pictures of the modeling
software that I used.

Thanks to everyone who has helped out so far! I just attended the JSHS
conference last week and was named "Regional Semifinalist." This
project also enabled me to win 1st place at our local district science fair
held for the first time this year. I really couldn't have been as successful
as I am now without the support of all of the experts and other contributors.

Sincerely,

BB