Visitor of the Week: Merissa Xiao

Meet Merissa Xiao of the Van Andel Institute. The postdoc in Dr. Huilin Li’s lab is at Protein Homeostasis in Health & Disease. This is her first meeting at CSHL and she found it “more efficient and convenient to meet and talk with people than virtual meetings. [She] felt the passion, perseverance and critical spirit of science from those attending the meeting.”

Tell us about your research.
My research focuses on understanding the mechanism of protein degradation, disaggregation, refolding and signal transduction in Mycobacterium tuberculosis (Mtb). During host infection, Mtb encounters various stresses that result in reversible or irreversible damage to proteins, leading to protein misfolding or aggregation. Molecular machinery, such as proteasome-mediated degradation, heat shock protein (Hsp100, Hsp70 and Hsp40) mediated protein unfolding or refolding, and two component system (TCS) mediated regulation of gene expression. Given the importance of the molecular machineries in Mtb virulence in the host, these proteins may present as potential drug targets for TB chemotherapy.

How did you decide to focus on this area/project?
I have been working on the Mtb system--and have been interested in this research field--since I was a graduate student. Starting from then, I was very interested in this research field. Dr. Huilin Li and Dr. Heran Darwin’s lab have been working on the mechanistic studies of potential drug targets in Mtb for many years, which they have reported many exciting findings. Though, there are still many things that need to be addressed, considering the resistance and multi-resistance occurring in Mtb. Continuing from my previous research, I want to dig into this system on the basis of current findings.  

What and/or who is the inspiration behind your scientific journey?
My long scientific journey was inspired by those who mentored me during my PhD and Postdoc studies, as well as by the research itself. The efforts of my mentors to elucidate the mechanisms of molecular machineries in Mtb and their exciting discoveries inspire me to figure out more from this system and ultimately contribute to the drug design and development of Mtb.

What impact do you hope to make through your work?
I would like my work to be significant, unique and useful. I hope the systems work well and our findings lead to more drugs being developed for the benefit people suffering from tuberculosis.

Where do you see yourself in five years?
I would like to move towards becoming an independent researcher on the basis of being fully skilled and qualified. I hope five years worth of research will allow me to have quality publications and to have a social network with top scientists in my research field.

What do you love most about being a researcher?
Doing research shares some common aspects with living:  raising questions, making plans and solving the problem. The process of problem solving could be very tough but through reading and investigating papers, I learn, get inspired, and experience. Other people’s findings help us and our research, in turn, will help other people. That’s the way scientific research moves forward.

What drew you to attend this meeting?
Protein Homeostasis in Health and Disease meeting held by CSHL is famous in this research field. There are intensive talks by great scientists from all over the world. It is a great opportunity to learn new techniques from the talks and posters, and to meet with people.

What is your key takeaway from the Meeting; and how do you plan to apply it to your work?
My key takeaway is regarding scientific thinking, writing and presenting. I was motivated by the passion of the other participants, and I would definitely like to keep scientific thinking active and critical through my research career. I also received useful suggestions for my project and, such insight will definitely help me and my research going forward.

What feedback or advice would you share with someone considering to participate in this meeting?
I highly recommend people attend this meeting. The number of fantastic talks is astounding that it can sometimes be difficult to keep up.  The active and passionate atmosphere greatly facilitated scientific communications. Prepare to return to your lab inspired and teeming with new techniques and knowledge.

What’s the most memorable thing that happened during the Meeting?
The most memorable thing is meeting and talking to the speakers, whose papers and books I have frequently read and online seminars I have attended. They provided with very valuable suggestions that motivated me a lot.

What do you like most about your time at CSHL?
I like the academic and historic atmosphere in CSHL. The landscape is also amazingly beautiful. All the buildings have special names (after famous scientists) and there are pictures of famous scientists on the walls of the canteen. Walking around CSHL inspired me and my work a lot.

Thank you to Merissa for being this week's featured visitor. To meet other featured researchers - and discover the wide range of science that takes part in a CSHL meeting or course - go here.

Image provided by Merissa Xiao

Visitor of the Week: Dan Smethurst

Meet Dan Smethurst of the Rowan University School of Osteopathic Medicine! The United Kingdom national is a postdoctoral research fellow in Natalia Shcherbik and Dimitri Pestov’s lab. He spent the latter half of this week at this second virtual CSHL meeting in 2020: Protein Homeostasis in Health & Disease. He again presented a poster and the one he presented this week is titled “Iron-mediated degradation of ribosomes under oxidative stress is attenuated by manganese”  

Tell us about your research.
In our lab we are interested in what causes damage to ribosomes, and the impact it has on their ability to accurately and efficiently synthesize proteins. My research looks into factors that affect the stability of the ribosome, and how this can cause it to malfunction and contribute to pathological states such as neurodegeneration.

How did you decide to focus on this area/project?
My work has focused on several different ways that cells respond to chemical and environmental stresses, and I became interested in how stresses affect translation as so many processes depend upon it. Previous studies from our lab demonstrated a fascinating interaction between metal ions, oxidants, and the ribosome, which connects the evolution of life on earth right through to major diseases of current clinical significance.

What and/or who is the inspiration behind your scientific journey?
Helping even to solve a small part of a puzzle can be incredibly gratifying, and there is no shortage of difficult questions to be asked in biology. The motivation in basic research is trying to uncover and explain something that has never been understood before.

What impact do you hope to make through your work?
I am glad to just contribute to the advancement of the field, and if something I have worked on ends up helping other scientists or clinicians that is even better.

What do you love most about being a researcher?
I enjoy the freedom to pursue the questions that interest me, and the colleagues and the community who support that and are so enthusiastic about seeing progress.

What drew you to attend this meeting?
There are so many great scientists presenting their work at the meeting and as my work is becoming more focused on the links between translation and disease, I thought this would be a good way to get a current picture of the state of this field.

What is your key takeaway from the Meeting; and how do you plan to apply it to your work?
I’m really impressed with the excellent research that has been presented so far. Perhaps the biggest lesson I am taking from it is how well-structured projects can enable impactful answers to be found through incremental experimentation. It has been making me think a lot about how to approach my research questions.

What feedback or advice would you share with someone considering to participate in this meeting?
I would absolutely recommend it, and I know everyone says this but I would encourage participants to ask a lot of questions and engage as much as possible.

What’s the most memorable thing that happened during the Meeting?
We are only halfway through the meeting, but I was fascinated by Ursula Jakob’s presentation in the first session showing that stochastic redox states of nematodes in their early life stages has a dramatic effect on their longevity and stress resistance later in life.

Thank you to Dan for being this week's featured visitor. To meet other featured researchers - and discover the wide range of science that takes part in a CSHL meeting or course - go here.

Visitor of the Week: Celia Deville

Meet Celia Deville of the Birbeck, University of London (United Kingdom). The postdoctoral researcher is a member of Helen Saibil’s lab in the Institute of Structural and Molecular Biology, a joint institute between Birbeck and University College London. The CSHL first-timer was on campus for the 2018 Protein Homeostasis in Health & Disease meeting where she presented a poster entitled “Structural pathway of regulated substrate transfer and threading through the Hsp100 disaggregate ClpB.”

What are your research interests? What are you working on?
I’m interested in understanding how some chaperone re-solubilize protein aggregates in the cell. I currently study a Hsp100 protein and use cryo-electron microscopy to characterize its structures in different states to understand how it can disentangle protein aggregates.

How did you decide to make this the focus of your research?
I became familiar with the problems of aggregation of unfolded or misfolded proteins during my PhD when I studied disordered proteins using nuclear magnetic resonance spectroscopy. This resulted in my becoming interested in the mechanisms involved in prevention and reversal of protein aggregation, and disaggregates are fascinating proteins machines for a structural biologist!

How did your scientific journey begin? 
I initially studied physics and chemistry, and was interested in the molecular mechanisms behind chemical reactions. I fell into structural biology because proteins are amazing molecular machines able to perform complex tasks in a specific and highly-regulated manner. More specifically, I’m interested in the importance of dynamics and conformational changes of the macromolecules driving biological processes.

Was there something specific about Protein Homeostasis in Health & Disease meeting that drew you to attend?
I work on protein disaggregation so the topic of the meeting along with the fantastic line-up of speakers drew me to attend. It is also a great opportunity to informally discuss recent results with researchers who apply a wide range of techniques to a common set of questions.

What is your key takeaway from the meeting?
It’s all a question of balance, which isn’t surprising when you are talking of homeostasis! It is fascinating to see that protein quality control mechanisms can be both very general and finely-tuned to adapt to certain substrates, stress conditions etc.

How many CSHL meetings have you attended?
This is the first CSHL meeting I have attend, and I very much enjoyed its program and organization on protein homeostasis so I would love to attend again in the future.

If someone curious in this meeting asked you for feedback or advice on it, what would you tell him/her?
I would definitely recommend the meeting to anyone interested in chaperones and/or protein homeostasis. This meeting will broaden your views and allow you to meet experts developing new methods and models to understand the general questions of the field.

What do you like most about your time at CSHL?
I really enjoyed the science and non-science related exchanges with the other meeting participants. The atmosphere is relaxed and people are very accessible – no matter their career level.

Thank you to Celia for being this week's featured visitor. To meet other featured scientists - and discover the wide range of science that takes part in a CSHL meeting or course - go here.