Next week on Friday, September 16th, our first seminar of the year is scheduled to be given by Dr. Lorimer. As of today, she has not provided a title for her presentation. Jamielynn, however, will initiate our discussion. I look forward to reading your responses.
NOTE: Today (9/14) Dr. Lorimer sent me the following title - "Mitochondrial DNA Replication and Recombination in Yeast." She also provided me a paper for background reading that can be downloaded from the following URL:
Dr. Lorimer’s presentation largely covered the functions and characteristics of the mitochondria and the importance of mitochondrial research in terms of human diseases. She also discussed methods being used on yeast to study changes to specific genes, however she did not put much focus on this portion of the presentation and I wish it would have been discussed a little more clearly.
ReplyDeleteAs for a question, I was wondering if anyone had any opinions/ideas on how yeast bacteria can continue to be studied to apply to human diseases such as MELOS (i.e. is there any way we can prevent mitochondrial diseases and increased mutation rates with age? How can knowledge of gene expression help us treat disease?, etc)?
I think studying mtDNA using yeast as a model organism will help us clarify how and which genes are turned on or off for certain diseases caused by mutations to mtDNA. The more we study gene expression in mtDNA in yeast, the easier it will be to apply what we learn to humans. This information will allow us to possibly design drugs or other therapies to prevent or slow the processes of mitochondrial diseases. We could target genes that we find in yeast mtDNA that cause mutations and block the expression of those genes, or also allow certain genes to be expressed depending on the data. I also read about the potential to transplant the nuclear genome from an oocyte of an affected woman to a healthy donor, which would allow the child to be related genetically but not have the mutated mtDNA transmitted. Granted this is just a potential therapy, but I find it a very interesting idea.
DeleteThat nuclear genome transplant seems extremely interesting. I had never heard of that before. That sounds like it could definitely be a potential therapy in the future.
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DeleteThe extensive applications of CRISPR-Cas9 in gene editing should be applicable in fixing mutations in mitochondrial DNA, mutations that are the culprit for diseases such as MELOS. Obviously it is dangerous to be attempting to alter the DNA of affected patients' mitochondria in vivo because of its vital role in cellular respiration. A model system such as yeast is needed. Researchers should be able to introduce the CRISPR-Cas9 editing system into yeast cells. The article Dr. Lorimer provided uses a technique that forces the yeast to use their mitochondria, which would allow researchers to compare the function of treated yeast mitochondria with control yeast mitochondria.
DeleteI believe that we could use mtDNA to do gene therapy much like what has done with our genome. This article from nature, http://rdcu.be/kqC8, (I only read the abstract) shows the use of gene therapy in the mitochondria by engineering mitochondrial genes and introducing them to the nucleus.
ReplyDeleteI would look at nuclear DNA and see all of the preservation mechanisms present (ie. DNA repair enzymes, proofreading mechanisms..etc). Then I would see if any of those mechanisms were present in the mitochondrial DNA. If the genes are present in the mtDNA, then research could focus on trying to increase the enzymatic activity or if the genes aren’t present, look into introducing them into the genome with gene therapy. Ultimately, having more mechanisms to preserve the mtDNA would lead to less chance of a mutation being passed along to future generations. Understanding gene expression and the mediating regulatory factors provides insight into many degenerative or developmental diseases which would be needed in order to treat the disease and not the symptoms.
ReplyDeleteThis was exactly my train of thought. There definitely needs to be a focus on preserving the mtDNA to treat the disease and not the symptoms as you said.
DeleteHaving a complete understanding of mitochondrial inheritance is essential for prevention of a disease like MELAS. If my recollection of the accompanied reading is correct, parental yeast cells sequester mutant mitochondria while normal mitochondria are contributed to budding daughter cells. Perhaps if research focused on the mechanisms that cause this pattern of inheritance in yeast cells, then it could be applied to germ cells in human females. Researchers could use this knowledge to develop a medical technique that sequesters mutant mitochondria to polar bodies so that only normal mitochondria are present in the functional oocyte. This would not address treatment of MELAS-like diseases, but at least it would be an effective method for reducing the proportion of mutant mitochondria that are inherited by future generations.
ReplyDeleteThis is an excellent point. I had read through that and hadn't even thought of that. Being able to research methods of potentially sequestering mutant mitochondria and only passing along healthy, functional mitochondria would certainly aid in preventing or decreasing the risk of mitochondrial diseases
DeleteThese are excellent comments and a very fine discussion! This are exactly the types of responses I am seeking via this forum. Keep up the good work!
ReplyDeleteBTW, some of you have yet to contribute. C'mon - participate!
Baker’s yeast is a model organism for studying mitochondrial DNA, and is therefore an excellent way to study a variety of diseases affecting this DNA (which could lead to other symptoms/problems throughout the organism). I think the gene expressions associated with mtDNA present in the yeast could be used to compare what type of genes and proteins are passed down maternally in humans that causes mutations and, potentially, diseases/abnormalities in homeostasis. There are many diseases associated with ATP production, as well as other enzyme deficiencies, MELAS (excessive lactic acid), and, simply, aging. Since the yeast is such a good model organism, I think scientists could research the genes that are leading to these conditions and this could be used for learning more about the gene inheritance from mother to child that occurs through generations. This could lead to more efficient treatments or even cures for some of the diseases.
ReplyDeleteAs Dr. Lorimer stated in her presentation, Saccharomyces cerevisiae has been used as a model for genetic research for the past century. With that in mind, I think that with the immense amount of information available (complete genome, proteome, etc.) in itself allows for further determination of how mutated mtDNA in this fungus can be applied to human diseases. Specifically though, after comparative analysis to determine conserved sequences between human mtDNA and yeast mtDNA, knocking out specific genes would allow for an analysis of their function. This could lead to the determination of the cause and treatment of specific diseases in humans. In the talk it was mentioned that the M4R1 was one of the genes that is still being researched to determine its function.
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ReplyDeleteAlthough yeast are single-celled organisms, they possess a cellular organization similar to that of higher organisms, including humans. Because of this, I think continuing to study gene expression of mtDNA in yeast will help us apply any findings to human patients. By researching genes leading to conditions such as MELOS in other eukaryotic organisms, researchers could possibly find ways to treat related diseases in humans.
ReplyDeleteI like the idea of depending on/enhancing innate repair mechanisms (as Michael mentioned) to minimize the effects of mtDNA mutation, largely because it is most likely to be effective and least likely to cause side effects from my limited understanding. However, I think that the most influential advances in holistically understanding mtDNA function and expression will be resultant of the development of new tools/techniques. A specific (potential) example is the prokaryotic Cas system/CRISPR and associated proteins to more precisely target specific nucleotide segments for mutation/excision. I think that if an effective method of delivery were to be developed in conjunction with the optimization of producing tailored CRISPR/proteins, gene therapy could potentially be an option for individuals with mtDNA mutations.
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ReplyDeleteA large proportion of mitochondrial diseases are due to mutations in mt tRNA genes which can have variable severity. MELAS disease is caused by a point mutations in tRNA (Leu). One way to deal with MELAS is to partially suppress the levels of the mutated tRNA (Leu) is by overexpressing mitochondrial Leu-tRNA synthase. Similar research is carried out by Rorbach, J., et al., 2008. Overexpression of human mitochondrial valyl tRNA synthetase can partially restore levels of cognate mt-tRNAVal carrying the pathogenic C25U mutation. Nucleic Acids Res. 36, 3065–3074.
ReplyDeleteAs Sarah and Amina and a few others mentioned, I think it is a great benefit for us to be able to study Baker's yeast, as it is eukaryotic with mtDNA. Dr. Lorimer also discussed how it is cheap and easy to grow proving another reason to be a great resource for research. Taking advantage of studying yeast, I believe we can make steps in medical advancements. Just by studying mtDNA in yeast, we can learn more about mtDNA diseases, like MELAS as was touched upon on Friday, or even just diabetes, MERRF, and other health problems and hopefully gain a greater understanding and find cures.
ReplyDeleteDr lorimer’s research is very promising and merely covered mitochondrial as a structure and functional organelle. In particular, MELAS is a life threatening conditions that paralyse the whole body and through mtDNA modification may act as a specific therapy even to some incurable mutations.
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