Need Help on Project Idea!!!

[deleted-596717]

Hi everyone!

I really enjoy research and science (of course ), so this year I'm hoping to enter in some science/research competitions such as Intel ISEF, Regeneron STS, and the BioGENEius challenge. Here are my ideas:

Ideas:
1. This idea relates more to cancer, but can also relate to other diseases such as neurodegenerative diseases: Use modern biotechnology to understand the function of a gene expressed in mitochondria that is related to the calcium/potassium channels. (The gene will be one that scientists haven't looked into its function yet, but they know the location of the gene.) Since these channels play a role in triggering apoptosis in cells, by extension, we can understand this gene's role in apoptosis.

2. This idea relates more to stem cells: Same as Idea 1, with the exception that we would be looking at how this gene affects mitochondrial health- which is important because mitochondrial health is vital to stem cell function.

(I sort of got ahead of myself there since I've been thinking of the different directions to go with this project so some of it may sound overly optimistic )

Questions:
1. Are any of my project ideas are up-to-par to be competitive in the competitions mentioned above?

2. Which idea is better? 1 or 2? If my ideas aren't good, what should I do to change them and make them better?

3. There are so many unique projects at these prestigious competitions so how do I differentiate myself from the rest of the crowd?

Any advice is greatly appreciated!

Thank you!!!

Moderator note: I've moved this to the Grades 9-12 forum where those experts can help you decide on a project!

[SciB]

Hello and welcome to Scibuddies. I am happy to hear that you are aiming for these prestigious scifair competitions. As you said, you need some twists and creative jumps to stand out from the crowd. I can try and help.

Sounds like you are interested in mitochondria and they are extremely important little organelles. However, my first big question to you is what kind of a lab do you have access to? If you want to perform advanced research then you have to work in a research lab. You can't do this stuff on the kitchen table--usually.

Triggering apoptosis of cancer cells is a goal that scientists have been working on for years with mixed success. The problem, as usual, is how to target malignant cells while leaving the healthy cells unharmed. The human immune system is good at detecting abnormal cells and killing them but it does not always 'see' cancer cells because they are body cells that have gone bad. Training immune cells to attack cancer cells is one way to accomplish this but there are still some problems with the methods.

Mitochondria are good targets as they provide energy to cells so if you knock them down then the cell may die or at least go into resting phase. But how will you devise a trigger that only works on cancer cells--if that is your goal?

Send another post with more information on what sort of hypothesis you are thinking about and then we can talk better about what experiments you would need to do and whether you could find a way to do them.

Best wishes,

Sybee

[deleted-596717]

Hi Sybee!

Thanks for your response! I do have access to a research lab and the equipment.

My initial "hypothesis" was that I could delete gene that is fundamental to the synthesis of a protein channel in the mitochondria (ie. ion channels), so that as cancer cells replicate, the mitochondrial DNA of the daughter cells won't express this gene and therefore the cells would die. However the main issue is that because the first cell doesn't have this gene, it would mean that it could die before replication (so basically I would only destroy one cell, which isn't really all that useful).

An idea was to find a way to amplify this process so that it can target more cancer cells, but that would be something that will take many years to figure out and would require lots of resources -- which I can't obtain because I don't have funding.

I've decided to shift my focus a bit, and I'm wondering if it would be just as unique/interesting if I studied a function of a gene that is integral to the function of the mitochondria? It would be a gene that scientists know exist within the mitochondria (preferably associated with the ion channels, since that's what I'm most interested in), but no one has really gone far enough to study its specific function.

Let me know what you think, as well as any other suggestions you might have.

Thank you so much!

[SciB]

Hi and sorry I missed your last question.

Have you decided on a specific aspect of mitochondrial function to do your project on? If you are interested in targeting cancer cells, you need a specific marker to distinguish healthy cells from cancerous cells. Since all cells have mitochondria and need them for survival, targeting mitochondria is not going to work unless you can somehow link it to tumor cells.

This has been the problem of cancer researchers for decades--how to kill tumor cells with minimal harm to normal cells. Chemotherapeutic drugs do kill cancer cells but they can also harm normal cells and that can have all sorts of bad side effects.

In your last post you talked about looking at some mitochondrial gene product that has not been well characterized. Did you find something interesting there? Post again with your latest update on the project and I will try to help.

Sybee

[deleted-596717]

Hi Sybee,

I think developing a marker to target specifically cancer cells will be relatively difficult —especially since it's troubled scientists for decades, and I'm only in high school. I also don't have the necessary equipment nor funds to do this type of research.

On the other hand, I'm also interested in genetics, so I've been looking at specific genes that are not studied much and their function in the mitochondria. (I had initially looked at genetics and tried to find a gene in the mitochondrial inner membrane that deals with ion-channel regulation in efforts to link its function with apoptosis, hence relating this function to cause the destruction of cancer cells.) After a month of experimentation, I've found a gene in the mitochondria that people know exist, but there are not any research papers published about its function.

Long story short, I think switching my idea will be best. For this new idea, I'm hoping that understanding this "new" gene's function will be somewhat unique. After I determine the gene's function, maybe I can link it in to a broader discussion? For example, *if* I find that this gene is vital to mitochondrial survival because it causes protein misfolding if deleted, then I could potentially link this in with some disease caused by this mitochondrial protein misfolding.

There are definitely some issues still with this idea since it is overly optimistic. However, I'm hoping you could help make it more realistic/feasible as well as provide any other suggestions? Especially regarding the potential results, will my new idea be novel enough (at least for competitions like Intel ISEF, Davidson Fellows Scholarship... etc.)? Let me know what you think.

Thanks!

[SciB]

Hi,

Sorry to take so long getting back to you. I did not see your reply until today.

OK. Sounds like you have made some good progress towards at least a potential project. There are still a lot of details that I need to know before i can advise you about how best to proceed. I am assuming that you are using cultured cells of some kind--correct? What are they?

You said that researchers have already identified the gene that you are working with. What is it? A lot depends on what the gene is known to do in a cell. If there are no papers about its function then you can be the first to look for what it does. One way to do that would be by gene silencing which is a technique that uses a specific RNA sequence to shut down translation of a protein. When you knock out a protein then you can look at various cell functions and see which ones are affected. It's a fairly time-consuming method when you don't know what the protein does, and can be rather costly for reagents.

You said that the protein might be involved in preventing protein misfolding so that would be a good place to start. I would get the DNA sequence of the protein and do a search to find out what its similarities are to other published sequences. This may give you some clues as to its functions and potential regulation.

Post again with some more information about your cells and protein and I will try to help steer you into a prize-winning project.

Sybee

[deleted-596717]

Hi Sybee,

Thank you so much for the advice!

I'm currently using HeLa and HEK cells to study this gene's function. Since it's a gene expressed in the mitochondria and it has no publications on it, I'm mostly focused on studying its function through gene knockout/knockin using CRISPR/Cas9 (I've read that this is a very effective and reliable method). This will hopefully allow me to evaluate the gene's functions by observing what happens when the gene is not expressed, when it is overexpressed, and when it is expressed.

However, I'm wondering if this will be a project that would be worthwhile to try to take to a major competition since application form deadlines are coming up? Let me know what you think.

Thanks!

[SciB]

Hi,

I guess the first thing I would ask is: What's your hypothesis? People entering major science fair competitions have very clear questions that they are asking. The experiments are important, but they are secondary to the hypothesis. In your case, unless you have a good idea what your mitochondrial gene does, based on some evidence like sequence homology to a known protein, then they will not give much weight to such a project. If, however, you do preliminary experiments that identify the protein's function as playing a role in apoptosis, protein folding or as an ion channel, you might be able to work that into a good hypothesis that you can test.

I wonder what you will test for if you don't know the function. You can use CRISPR to alter the target gene, assuming you know its sequence, but unless you know its function, I don't see how you can decide what to look at.

Have you done a BLAST search for your protein to look for homology to known proteins? That is something that needs to be done. Are you sure that nothing has been published about your protein? Sometimes researchers independently 'discover' the same gene product and just give it a different name until someone else finds out that the two proteins are the same.

I can advise you, but I need more information. Unless you can state a workable hypothesis, your chances of success in a major scifair are small, in my opinion. These competitions are judged on high standards by scientists who look for a clear and logical hypothesis, appropriate and workable plan of experiments and sound statistical evaluation. And these are the minimum requirements. If you want to be a winner, you need something more.

Post again and I will try to help.

Sybee