IAMA 3rd year Ph.D. student researching the cell biology of the Rice Blast fungus, Magnaporthe oryzae, and preparing for my candidacy qualifying exam. AMA.
Hi Tilders! I am new here, but my experience with the community thus far has encouraged me to post an AMA. I've specifically decided to post this AMA in ~talk rather than ~science for more exposure, and because I am hoping to field questions ranging from scientifically well-read to less-read, technical to curious, why care to who cares, and everything in between.
I won't be posting "verifying proof", because like many of you, I love my anonymity here. However, I will include peer-reviewed citations to question answers when I feel it necessary. I will do my best to share free-access articles, but this won't always be possible. If I link an article of interest to you that is paid-access, message me; maybe, I may be able to get a copy to you. Also, please be patient for my replies. Even though it is summer where I am, I am still busy in the lab and thoughtful responses take time.
Here is a brief background on the Rice Blast fungus to help get the conversation started:
Rice is an important staple food consumed by nearly half of the global population Khush. 2005. From 10 - 30% of the annual rice harvest is lost to disease caused by Magnaporthe oryzae, which is enough rice to feed greater than 60 million people Skamnioti and Gurr. 2009. To cause infection, a three-celled asexual spore called a conidium attaches to the rice plant's leaves, stems, and even roots. Once attached, a germ tube emerges from one of the three cells and grows along the surface of the plant. Hydrophobic molecules on the plant surface, called hydrophobins, induce a developmental change in the growing germ tube. The growing germ tube tip begins to form a dome-shaped structure called the appressorium. This specialized structure swells and generates up to 80 Mpa of pressure, enough to penetrate kevlar. A penetration peg penetrates the plant cell tissue, and bulbous invasive hyphae colonize the plant cell tissue. The fungus keeps the invaded plant cell alive, while it consumes its nutrients, with the plant cell dying only when the invading growth moves to an adjacent cell Cruz-Mireles et al. 2021. Schematic.
The Rice Blast research community focuses on all stages of its development. My work is focused on nuclear division during different developmental stages, and I am specifically working on understanding which and how motor proteins are involved in nuclear division in this fungus. Understanding the nuclear dynamics and the involved machinery will hopefully open avenues for controlling the plant infection and reducing the global crop loss.
I hope you all find Rice Blast interesting, and I hope I will be able to answer many interesting questions!
What is something you found in your research that you think would be surprising for the average layperson?
Fungi and animals are more closely related to each other than either are to plants. The motor proteins found in fungi are the same as the motor proteins in animals (though fungi tend to have fewer copies and are even missing some that are found in animals). My recent work has found motor protein inhibitors that work superbly in animals systems, do not work in fungi (and vice versa). There is also great variability in the amino acid sequences of the same proteins within fungi, suggesting drug specificity could even be fungal species specific. This is exciting news to me, because I previously did work on azole resistance development in Aspergillus fumigatus. Azoles are used in the clinic and in the agricultural setting to fight human and crop pathogenic fungi, which has led to people acquiring azole resistant fungal infections without ever being treated with the fungicide. The disconnect between the specificity of these motor inhibiting drugs suggests there is a diminished concern a similar issue could arise from the use of fungal motor specific drugs. Confirmation of drugs used to control M. oryzae are specific to M. oryzae and not to human fungal pathogens will be an important step in future fungicide development.
EDIT: I had just posted this topic and was about start a microscopy session. See bold corrections!
Hopefully this question makes sense given my complete lack of knowledge of fungi:
After the fungus fully occupies the initial epidermal cell and invades an adjacent cell, does the fungus 'stay' in the initial cell? Do the buds break off into their own separate body, or do they all stay connected? I imagine the cell wall of the original cell degrades and loses integrity after the cell dies, making it easier for the fungi to 'stay together' as a single unit?
Since you mentioned that fungi have motor proteins, what do the motor proteins do? The only thing I really remember of motor proteins is that they're used for muscle contraction, but that's not exactly something fungi have.
Best wishes on your quals. It’s an interesting topic.
Questions:
Answers:
Given this is in talk not science I hope this question isn't too out of line, but given the popularity of things like the Last of Us what are your thoughts on a Fungus apocalypse? From a pop culture prospective or as an actual threat.
I am a huge fan of Last of Us, the game and tv adaptation. There would need to be a large leap for Cordyceps to adapt to humans. To this date, mycologist have not found something like the "zombie ant fungus" in fish, amphibians, or mammals. I don't expect a fungal apocalypse to be anything like zombification. We do get infected by fungi, and infections and deaths are on the rise, but these are generally limited to immunocompromised people. Only a few fungi are capable of surviving our high body temperatures, and even of those depend on a sick immune system to take hold.
So as for apocalypse level scary, I think bacteria still hold the reigns for most likely to wipe us out, behind of course, us wiping us out.
Are there any strains of rice that are naturally more resilient to the Rice Blast fungus? Have there been attempts to breed or genetically-modify such a strain?
What led you to choosing this for your research? And, it seems, the interest in fungi generally?
Honestly don’t know anything about this field but it sounds interesting. That said this question will have nothing to do with the what you are researching but it’s mostly about how you are doing the research.
About three years ago Google's DeepMind announced AlphaFold 2 which was hailed as a big breakthrough in protein folding, have you used it or any other Ai models to help with your research? There was a lot of hype when AlphaFold was announced but I haven’t seen much news about it being use in real research yet. I know it was used to identify(?) COVID spike protein but that was the last thing I remember anyone doing anything with it.
How are you feeling on your qualifying exam? Do you have any plans to take a break after?
I'm finally getting back around to answering questions again. It's been a hell of a couple of weeks in the lab.
Well, I've passed the written portion already, but I still have my oral exam. I'm feeling better having half the process finished. A friend in my program reminded me the fear is manufactured, but that doesn't take away from the idea the past 3 years can be for nothing if I fail.
Congrats on getting that much out of the way! I think that's a good way of looking at it. I've viewed it as "If you prepare for it you are the expert in the room on this topic, but you have to prepare for it."
Don't be afraid to say you don't know something if it's a super specific question, but always have an idea on where you could find out the information. Also, don't be afraid to take a moment to consider what is being asked of you, or to even ask for that moment.
What is the format of your QE? I just passed mine (Physics PhD candidate here) and mine was an oral exam. A 45 minute presentation on my research followed by roughly 2 hours of questioning. It was stressful but I passed. Wishing you the best of luck on yours! It's such a relief to get out of the way.
I'm heading towards a statistics PhD but am at an earlier stage than you. Can I ask you if you also had written quals? During the course of our program we have 3 written qualifying exams (based on the contents from 7 classes total-- two exams cover two classes and one exam covers three). Then later on there are two oral exams (I'm have not learned about the content/format of it).
I haven't taken any of the exams yet, but am studying. If you had written exams, how was the experience?
We had written "prelim" exams which you completed prior to the beginning of second year. These basically just covered coursework. I didn't find them that bad. It was two days of exams, basically two afternoons, and each exam had two questions per subject (for physics that would be things like classical mechanics, quantum mechanics, stat mech, etc). I actually found the prelims harder than the qual, partially because the quals were on my research and therefore what I've spent most of my time thinking about.
In my case the questions on the written exam were fair, certainly no harder than what you might see on a final in one of those classes, but the variety of topics one had to be familiar with made it difficult.
Yes, our written quals are preliminary.
In our case, four of the seven classes covered are classes that are filled mostly with master's students, so in those cases there's a "watered down" class final (for the master's students) and then the qualifying exams are more reflective of the rigor expected from a PhD student, which unfortunately means that the finals are typically not good prep for quals. Fortunately my school posts questions from previous exams for practice, so we have an idea of what they're looking for.
Overall it doesn't seem too bad, but as someone who's a master's student transitioning to a PhD, there's a time gap between when I took the classes and when I'm taking the exams which causes me to be rusty unfortunately.
Additionally, I've spent the past year working on a master's thesis that relates to almost none of what was covered on the exams, to I have to go back and review everything.
The upside to this is I definitely am gaining a more in depth understanding of the material the second time around, which I believe will serve me well in the future.
I'm finally getting back around to answering questions again. It's been a hell of a couple of weeks in the lab.
My QE format is written exams from each of my committee members (passed), and an oral exam within 6 months of passing the writtens. The oral exam consists of an oral presentation of a written research proposal followed by 2-3 hours of questioning. I'm so ready to be past it so I can get on with my work. The idea that failure at this point means the last 3 years have been for naught is absolutely terrifying.
May God help you.
Mine was a disaster area. Five questions. Seven days. So, so open ended (I'm an engineer, so I'm curious how you're different).
My co-advisors were good enough, but these were still long, long questions. I at least knew them well enough to know what they were after.
The middle person was a horror. I thought I answered the question, but it was just so generic. It turns out she wanted some other answer, but that's not what my PhD is in. It got resolved with me learning some new stuff (good ending for those of us who eschewed money for science. I've done well for family.)
Two of the people were there for departmental reasons. One was good enough. Still day long, but good. The other was just a hot mess. I did what I could and heard nothing back.
Anyway. It sucked.