Blue Devil Pride!!!
Since I am a Duke alum, I am very excited that one of Duke's Biochemistry professors, Dr. Paul Modrich, is a co-recipient of this year's Nobel Prize in Chemistry. While I was at Duke Medical Center, Dr. Modrich's lab was below ours in the Nanaline Duke building. I was just a grad student doing rotations at the time, but I found Dr. Modrich's lectures to be very interesting, and he was (and I assume still is) a very nice man. I had friends and colleagues who either rotated or worked in his lab, and every one of them only had the highest praise for his lab's environment.
It should be noted that he is sharing this year's prize with Dr. Tomas Lindahl from the UK and Dr. Aziz Sancar from the University of North Carolina-Chapel Hill--see it is possible for a Blue Devil and a Tar Heel to collaborate! (The first video below is a brief interview of Dr. Modrich.)
Dr. Modrich's research focuses primarily on the Mismatch Repair mechanism (MMR) that fixes mistakes that may arise during DNA replication. It is incredible to believe how high the fidelity of DNA replication must be when the chromosomes are being copied. Even the smallest of mistakes can be deleterious. A mutation in the MMR pathway is the most common cause of hereditary colon cancer.
MMR is not the only repair pathway for DNA. For those of you who have taken my Chemistry of Cancer class, you should (hopefully) remember that we discuss the MMR pathway as well as other repair pathways and mechanisms, including nucleotide excision repair (NER) and base excision repair (BER). If any of these pathways become erroneous, then the results can include carcinogenesis or cell death. A video of the DNA repair mechanisms by the Khan Academy is included below.
After reading this, I was curious as to what exactly Dr. Modrich had discovered in regards to the mismatch repair mechanism. The Nobel Prize's website gave a satisfactory answer to this question (http://www.nobelprize.org/nobel_prizes/chemistry/laureates/2015/advanced-chemistryprize2015.pdf). DNA mismatches occur when base pairs match up in ways other than A-T and C-G. The first line of defense against such errors are endonucleases that 'proofread' the newly-made DNA strands and correct mismatches. Mismatch repair occurs to deal with errors missed by the endonucleases.
ReplyDeleteDr. Modrich's work, according to the Nobel Prize site, builds upon work by earlier geneticists. Robin Holliday had first proposed that DNA molecules would experience mismatches and require correction, and experiments in E. coli bacteria showed that the bacteria fixed mismatches in DNA strands introduced by viruses. However, it was not known how they accomplished this. Geneticists Robert Wagner and Matthew Meselson observed that the fixes of mismatches tended to occur on the same strand, and suggested that the mechanism was strand-specific. They also suggested that this process could be directed by methylation, as a newly-synthesized strand lacked methylation. Observations of E. coli that lacked enzymes for methylating DNA showed that these bacteria had higher rates of mutations. Other geneticists discovered genes required for methylation. Modrich's work found direct evidence for the methylation-mismatch-repair link. Working originally in concert with Meselson, and using E. coli as subjects, Modrich's work culminated with a paper explaining the results of an experiment where he combined the genes required for methylation with DNA binding protein and the different enzymes (DNA ligase, DNA polymerase III, and exonuclease I) and showed how the mixture could repair the mismatches in DNA.
Correction: the different enzymes (DNA ligase, DNA polymerase III, and exonuclease I) that his previous work had shown were necessary to mismatch repair...
DeleteTo begin with, congratulations to Dr. Modrich and his reward. I can only imagine the passion and love for science he must uphold to have gained the respect of earning a Nobel Prize, in chemistry no less! I am amazed by the way the body has a natural correction system, especially when considering DNA which is one of the fundaments of life. The Lord had such a care for how He made us humans (and other living organisms) to automatically and involuntarily integrate such a system. Such precision, such complexity, and such a masterpiece. I have not had the opportunity to understand and dedicate time to the three single stranded mechanism, nor the three double stranded mechanisms of DNA correction, but it is definitely something I hope to appreciate and understand once the opportunity arises!
ReplyDeleteFirst, Go Blue Devils! That was my first choice for an undergraduate education, but obviously God led me to SEU! Secondly, congratulations to Dr. Modrich on receiving the Nobel Prize in Chemistry!! I'm sure the award is well deserved. I'm also sure that he is very excited to see years of research and dedication pay off.
ReplyDeleteHis discovery is quite intriguing especially when we discuss the potential uses for it. He mentions how the MMR pathway is found to be the common cause of colon cancer. I have only talked about DNA repair only in the context of Genetics and a few other classes so my background is not that extensive. I would be interested though to see what else would come from the results of this research and how it could be used to find cures for various diseases.
Wow, big congratulations to Dr. Modrich for the Nobel Prize! I couldn't imagine how it must feel to receive such an honorable reward. It is absolutely incredible to believe God has created such an intricate system in our bodies. The fact that he created a correction system for when problems do arise shows how great the mind of our creator is! While I have heard often of colon cancer, I never knew of it's connection to the MMR pathway. Mutations in the body always make me very curious. It is hard to wrap my mind around the idea that mutations and mistakes can occur in such a perfectly intricate system. However, it is amazing to see people like Dr. Modrich who dedicate so much time in their lives to pinpointing the origins of these errors and trying to figure out a way to change it. We are so blessed that when things do go wrong, God gives us the knowledge and opportunity to fix it ourselves!
ReplyDeleteCongratulation to Dr. Modrich for his amazing accomplishment! I can only imagine how he must feel for having such a high honor. Personally, I do not know much about what all his studies entails as I am not that high up in my education yet. When the time comes for me to learn such things, however, I will always remember this man and his work. I am eager to learn more about this subject so that I may have a deeper level of appreciation and knowledge, but for now, I just want to again congratulate Dr. Modrich. Also, I would love to see the latter results and how that will affect the health/science world.
ReplyDeleteFirst off I want to start off this blog post with a huge congratulations to Dr. Aziz Sancar because he is the one that is representing the best college in the state of North Carolina. But in all seriousness congratulations to Dr. Modrich. The Nobel Prize is in my opinion the highest honor any scientist or individual for that matter can ever hope for. The work that Dr. Modrich is being recognized for is something that I am not familiar with. However, I am familiar with the process of DNA replication and the importance that process has in biology. So the fact that Modrich's research is in such an important part of the biological process is even more reason to celebrate this amazing achievement. I look forward to continuing in my career of the sciences so that I can gain even more appreciation for the work that is done. All in all a massive congratulations to Dr. Modrich, Dr. Lindhahl, and Dr. Sancar. All though the idea of Duke and The University of North Carolina being on the same team still astonishes me, I am sure that North Carolina will show there superiority on the basketball court, just like they always do!
ReplyDeleteUNC...the best college in NC? Blasphemy!!!! :)
DeleteA HUGE congratulations to Dr. Modrich for the incredible accomplishment. I was recently reading about the Nobel Prize winners and it's crazy to think you are familiar with one of the individuals who was the recipient of it. Having a taste in DNA replication and the repair process involved with Dr. Schraw's Genetic and Cell-Molec classes, I can appreciate the significance of the work achieved by Dr. Modrich. I hope that as scientists can continue to increase knowledge in the realm of DNA replication and repair, medicine can develop new methods against genetic disease. Understanding replication and repair in MMR pathways is a huge step in developing techniques to help people all around the world. This is truly inspiring work.
ReplyDeleteFirst off congratulations to Dr. Modrich, it is a greater honor to be bestowed the Nobel Prize. However, the significance of his accomplishments is not only that the Nobel Prize was obtained but also that Dr. Modrich was able to help so many people out there with this discovery. With the mutation of the MMR pathway being the leading cause of heritable colon cancer Dr. Modrich has played a significant role in potentially saving millions of live, thus the beauty of scientific research. It’s amazing to see science still progressing and working towards fixing all of things that the average person would have no idea about, and helping millions.
ReplyDeleteAfter reading this post I immediately brought up PubMed to look for the articles that Dr. Modrich contributed to. I was bombarded with about 174 articles with most of them being on DNA Mismatch repair or DNA excision repair. After browsing a few of the abstracts I gained a glimpse at just what goes into keeping our DNA free of errors. I was also able to see for myself why his research was so important as to earn a Nobel Prize. I also noticed that the abstract mentioned that there are still some mysteries to be solved having to do with various parts that are unknown on whether they contribute or what they contribute to MMR. This is the link to the specific article I read. http://www.ncbi.nlm.nih.gov/pubmed/26283381
ReplyDeleteCongratulation to Dr. Paul Modrich when spending so much time researching something I'm sure it nice to be recognized for your results especially a Noble Prize. I've allows been amazed with the body ability to function the way we do. We have so much going on and one mistake can lead to not such good things. God is amazing to think how he has made us to live in this world. How are body has ways or checkpoint to prevent major mistakes. Dr. Paul Modrich is making the Duke and Blue Devil nation proud.
ReplyDeleteCongratulations to Dr. Modrich, that truly is a great accomplishment! His scientific research is inspiring and ground breaking. This research on MMR pathways opens up new doors for helping people all around the world.
ReplyDeleteIt is great to see great things come from the state that I consider to be a second home! Congratulations to Dr.Modrich on achieving such prestigious honor in the science field. His hard work has paid off and has made such a contribution to the field of genetics. It is always so fascinating to learn new thongs about the human body and how it functions. I have only been able to study this in general genetics and have not yet been able to study the material at a more scholarly level. I was intrigued by his statement about the MMR pathway being common in cancer. I hope that there is more beneficial research to contribute to genetic medicine.therapy!
ReplyDeleteCongratulations Dr. Modrich on your accomplishments. This just shows that hard work and consistency pays off in the long run. Also, thank you for being so dedicated to research in genetics.. It is greatly appreciated from those who lost all of their loved ones from cancer. It is fascinating to learn another pathway that can lead us closer to discovering how to prevent these diseases from progressing. Once again thank you Dr. Modrich and Congratulations on your success.
ReplyDeleteI can only imagine the extreme joy that comes with receiving the Nobel Prize. What a contribution these men have made to the field of science! Thank you Dr. Modrich, Dr. Lindhahl, and Dr. Sancar for all your hard work and for the knowledge that you have made accessible to the rest of the world. Gaining a complete understanding of mismatch repair will greatly benefit research of genetic disease. Understanding how mistakes occur in DNA replication will result in pointed research on how to correct and prevent them from happening. This will then lead to global health, feeding the hungry, and world peace (I wish). However, on a more serious note, people that suffer from genetic diseases, once a cure is discovered, can live longer and healthier lives. I hope this research spurs other researchers to delve deeper into the understanding of MMR.
ReplyDeleteCongratulations to Dr. Modrich! One of the main questions we ask ourselves while facing a disease is what is its origin ? The fact of knowing that a mutation in MMR can cause lynch syndrome is significant to know how to approach it. There is a high percentage of mutations in two genes called MLH1 and MSH2 are responsible for most cases of Lynch syndrome, but in a few cases the disease has been linked to mutations in other DNA repair genes, including MSH6, PMS1, and PMS2. (1) Usually patients with Lynch syndrome have a germline mutation in one allele of a MMR gene and the second allele is inactivated by mutation, loss of heterozygosity, or epigenetic silencing by promoter hypermethylation. (2) There are some studies being made on a vaccine to prevent lynch syndrome focusing on MSI-H cancer-associated FSP antigens as potential targets for immune therapy approaches. (3) This sounds like a promising future in preventing Lynch syndrome.
ReplyDelete1. (https://www.mskcc.org/cancer-care/risk-assessment-screening/hereditary-genetics/genetic-counseling/inherited-risk-colorectal)
2.(http://www.uptodate.com/contents/lynch-syndrome-hereditary-nonpolyposis-colorectal-cancer-clinical-manifestations-and-diagnosis)
3.http://www.ncbi.nlm.nih.gov/pubmed/23760517
The questions I tend to ask are why? If there is such a repair favored over another, why? It is not possible to ask a base pairs itself, but trends can be noticed and conclusions drawn to the best of out ability. Studies have not reached that far to my knowledge, and often times when they do it is only a best guess. It is interesting that a type of single strand repair is the leading cause of melanoma. Some are environmental factors while others are endogenous. Bot can make a a huge difference!
ReplyDeletePlease excuse the misspelling: "conclusions drawn to the best of our ability." and "Both can make a huge difference." Thank you.
DeleteA few things can be concluded from an accomplishment such as the one Dr. Paul Modrich received together with other colleagues: (1) To accomplish such a advancement in science nowadays requires years of investigation, passion and most importantly team work, (2) Make sure whatever you decide to study in depth, you are willing to study it, analyze it, test it, fail, test it again and keep pushing until you reach a breakthrough, because it takes years to reach such level of expertise (note Dr.Modrich fine white hair*) and (3) Know that no knowledge is useless knowledge. We learn more from our mistakes than from our victories, the secret is just not to make it a habit.
ReplyDeleteOther than inspiring, Dr. Paul Modrich accomplishment brought up a curiosity on the subject that also helped me study for our biochemistry exam. Attached is another educational video with further details on DNA repair mechanism. It highlights the importance and the mechanisms of DNA repair.
https://www.youtube.com/watch?v=mDxpQGMVY54
That is cool that one of your former Professors is getting a prestigious award. And the topic of MMR sounds pretty interesting too, especially since the condition I was born with was due to an error in DNA/genetic information. I'd like to hear more about MMR and other genetic repair mechanisms in class sometime.
ReplyDeleteWow that’s an extremely prestigious award. Congratulations Dr. Modrich! I found it interesting that you mentioned the likelihood of mutations in mismatch repair causing colon cancer. I came across a very interesting article pertaining to colon cancer and mismatched mutations. According to the article germ line mutations in mismatch repair genes cause hereditary nonpolyposis cancer (HNPCC). The tumors associated with this form of cancer tend to demonstrate microsatellite instability.1 Because mismatch repairs correct mutations, if there is a decrease in mismatch repair genes then there will be an increase in spontaneous mutations. Mismatch repair genes can become inactivated in human cells due to both hereditary and sporadic cancers.2 I found it quite intriguing to see a huge correlation between cancer and mutations in mismatched repair genes. It is easy to see why Dr. Modrich would do so much research on this topic, seeing how fascinating it is.
ReplyDeleteWorks Cited
1.Peltomak P. DNA Mismatch Repair and Mutations in Human Cancer. Environmental
Health Perspectives.1997. 105(Suppl 4): 775–780. PMC1470030.
2. Mechanisms and Functions of DNA Cell Repair. Cell Research 2008:18:85–98. doi:
10.1038/cr.2007.115.
How cool! It's amazing how much hard work pays off throughout time. I'm sure he has worked long and hard for this Noble Prize. Also, what an interesting topic to be looking into, it's pretty obvious that he has a true passion for it. Congratulations to him! Being able to discover the correlations between cancer and having mismatched repair genes is extremely mind boggling, because not a lot of us can grasp the concept at all, we often look for more obvious reasons.
ReplyDeleteIt is great to see how humble he is about winning such a huge award. As he stated in the beginning of the video, he never even imagined getting such a prestigious award. It will be very interesting to see the implications of this finding as it relates to colon cancer. I can't imagine how many people will be positively affected by this mans (and other researchers) work as it relates to mechanisms of action in cancer. Great job to Dr. Dr. Modrich!
ReplyDeleteI think it is amazing how long he has been doing what he is doing. It's awesome to see all the years he has put into science come together for him to receive this award. He was very humble about it as well which says a lot about him as a professor and scientist. I think for him to discover how DNA replication, cancer and MMR pathways relate is an amazing contribution to the scientific community. His accomplishment and the knowledge that he shows replication and MMR pathways makes me excited to learn more in my career as a bio/pre-med student. Congrats Dr. Modrich!
ReplyDeleteWow, what a high honor to achieve the Nobel prize. I am sure he and his family are very proud of what he has accomplished. I remember learning about the MMR, NER, and BER pathways in chemistry of cancer and being fascinated by how they work. It may sound cheesy, but I think these pathways are a true testament to both the greatness and humility of the Lord. In us, he created such an intricate way to store, copy, read, and make functional proteins from the vast amount of information contained within DNA through replication, transcription, and translation. Yet, even after literally creating all of that, he knew that his creation would not always run perfectly. Thus, he also created these various pathways to correct mistakes that occur. While he created such a greatly intricate system, he also created these repair mechanisms.
ReplyDeleteIts incredible to hear a man who just won the Noble prize exhibit such humility and thankfulness. With that being said, he and his colleagues made an incredible contribution to the scientific and medical community by making a connection between DNA replication, the MMR, NER, and BER pathways and a specific form of cancer. Through this fundamental research and discovery it gives hope to a treatment and cure for colon cancer, considered a serious step forward in the battle against cancer. I hope that this discovery is put to use and is applicable in the future.
ReplyDeleteFirst of all, congratulations to Dr. Modrich! It is incredible for someone to win such an amazing award and be so humble about it. To find a connection between DNA replication and MMR, NER, and BER pathways is such an accomplishment. His works will surely impact many people's lives in such an astonishing way. Dr. Modrich is an inspiration.
ReplyDeleteIt's always nice to see how much hard work pays off. Congratulations to Dr. Modrich. It's always interesting/good to hear of new scientific findings and research. I'm sure this finding will help many people and will aid in the continuation of research towards these pathways.
ReplyDeleteThat is so awesome! Congrats to Dr. Modrich on winning the Nobel Prize. His findings of the connection between DNA replication and MMR, BER, and NER pathways are very fascinating. I am sure this research will be used to help many people.
ReplyDeleteWow, that's pretty neat to say the least that you actually got to be a part of his lectures. I'm sure you learned a lot that you're now sharing with your classes. Though I'm not too familiar with the Mismatch Repair Mechanism (MMR), his research sounds really interesting and I'll have to look more into it because fixing mistakes that can happen during DNA replication is a BIG deal. I'm glad to see that he was rewarded the Nobel Prize for his hard work and dedication to the science field.
ReplyDeleteIn Immunology and Histology, Dr. McConchie always likes to point out God's awesomeness when we talk about the ways our bodies protect themselves. It really is amazing to know that this defense system extends beyond what we physically see like our waterproof skin to the microscopic antimicrobial enzymes on the surfaces of all our body's openings and the natural killer cells, or B and T lymphocytes that mark unwanted cells for destruction in the body. I mean honestly God thought of everything!! Even within compromised cells He gave them a way to correct DNA mutations or initiate cell death if things got out of control. And to think that there are still a lot of these mechanisms that scientists don't fully understand or that we keep learning new things about which goes to say that what we know could just be the tip of the iceberg in the "firewall" system God created. And He did all of this just to take care of us and keep us safe and healthy. Wow. Knowing He cares so much and attends to even the littlest details of our lives really helps me put things in perspective.
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