Born and grew up in Valencia, Spain, Dr. Cristina Puchades did her undergrad in Biotechnology with Honors in Research from the Polytechnic University of Valencia (Spain) in 2011. Her passion and motivation for research landed her into California, USA, with a Ph.D. opportunity at the Scripps Research Institute (TSRI), La Jolla, CA, USA, where she recently graduated in 2019. During her Ph.D., Cristina used cryo-electron microscopy (cryo-EM) to determine the first structures of mitochondrial protein quality control complexes trapped in the act of unfolding substrates, revealing the structural basis for ATP-powered protein degradation.Her recent review article describing the molecular principles governing the activity and functional diversity of AAA+ proteins, published in journal Nature, popularized her work around the globe. Cristina currently holds a postdoctoral position at the University of California San Francisco. Her interest lies in understanding how biological machines work and how they drive biochemical and biophysical processes to promote health and disease. Her dedication to studying protein complexes at a molecular level has thus far lead her to study and work both in academia and industry in 3 different countries and 2 different continents. As a postdoc, Cristina will combine structural, biochemical and cell biological methods to investigate the molecular mechanisms underlying the activity and drug-mediated regulation of membrane ion channels.
SoLS Corresponding Editor, Dr. Priyanka Mishra, Postdoc at University of Texas spoke with Dr. Puchades and discussed several interesting facts about her journey so far:
PM: How did you choose your career path? Did you always want to do what you are doing now or did something change your mind along the way?
CP: I don’t think I “chose” a career path, I just kept an open mind and tried to make the most out of every opportunity that arised. As a Biotechnology major at the Polytechnic University of Valencia (Spain), I enjoyed many different courses,from plant genomics to animal physiology and from bioinformatics to analytical methods. I didn’t have a defined research focus, but I knew I wanted to participate in a study abroad program to experience a different culture. When my Biochemistry Professor recommended me for a 6 month internship at the headquarters of Janssen (Johnson&Johnson) in Leiden (The Netherlands), I took the opportunity without hesitation. The company has a strong focus on infectious disease and vaccine development. For two years, first as an intern and later as a research technician, I studied the dynamics of antibody-antigen interactions using a wide array of biophysical methods, including mass spectrometry and circular dichroism. Our group collaborated extensively with the Wilson lab, a renowned lab at the Scripps Research Institute that uses X-Ray Crystallography to study antibody-viral antigen complexes at near-atomic resolution. Having become passionate about the protein structures’ relevance to the biomedical field, I decided to pursue a PhD in structural biology. While myoriginal plan was to learn X-Ray Crystallography, I realized soon after joining the Scripps graduate program that the “resolution revolution” in cryo-EM was fundamentally transforming structural biology and represented the future of the field. I saw huge value in gaining in depth understanding of cryo-EM and I thus decided to rotate and eventually joined the lab of Dr. Gabriel Lander, a front-runner in the field of cryo-EM, who is also a dedicated mentor and an inspiring scientist.
PM: On your PhD experience - How you describe facilitating experiences and strategies for your thesis writing?
CP: I wrote my thesis very much as if I was writing a paper, a very extensive paper:Chapter 1 was an introduction to the biological question and the technique,Chapters 2 and 3 were my results, which corresponded to my 2 first author publications, and Chapter 4 was my conclusion, where I explained how my findings had impacted my field of study in a broader sense. To keep myself motivated during this process, I agreed with my PI beforehand that we would publish my introductory and concluding chapters as a review. This provided me with a “sense of purpose” and allowed me to dedicate my undivided attention to thesis writing for a couple of months.
PM: What is the importance of the supervisory fit for a doctoral student’s satisfaction and success?
CP: I think finding a good mentor is one of the most important factors for succeeding in grad school, along with perseverance, determination and emotional maturity. The“right” mentor will be different depending on your personality and/or the stage you are at in your career. In my case, during my PhD, I really needed hands-on mentoring both from a technical perspective as well as for developing soft skills, such as scientific writing and communication. I therefore joined the lab of Dr. Lander, who, at the time, was an Assistant Professor that had a small lab and provided one-on-one mentoring in an almost daily basis. In contrast, as my postdoctoral advisor I chose Dr. Cheng, a very established Professor who provides access to lots of resources and is very hands-off, allowing me to design and drive my research almost independently in preparation for a future leadership position.
PM: The PhD Job Hunt for you? What are the challenges you find in anticipating a stable research career?
CP: I want to become a group leader, which I know is a highly competitive and challenging career path. I just started my postdoc and my plan is to continue to work hard,keep my eyes open for opportunities and try my best to take full advantage of the opportunities I may find.
PM: Motivation to hold a postdoctoral fellowship at the University of California San Francisco and work with your current supervisor Dr. Yifan Cheng?
CP: I met Dr. Cheng, an HHMI investigator whose lab uses state-of-the-art cryo-EM methods to study membrane proteins, at the 3D electron microscopy Gordon Research Conference in Hong Kong in 2019. In his free time, Dr. Cheng runs marathons and during the conference he organized a 5k at 6 am to help conference attendees suffering from jet lag get, literally, back on track. While running with him and some of the postdocs from his lab, it was immediately apparent that he is a great mentor who promotes people’s careers and that people are really happy in his lab. A postdoctoral position in a well funded, world-class lab with a good mentor and a friendly environment was exactly what I was looking for…and here I am. PM: Could you explain in lay terms the research you are currently involved in? What is/are this project trying to find out and the motivation behind it?
CP: I am currently working on structural studies of a family of transmembrane proteins called TMEM16. Members of this family, especially TMEM16A, have been directly linked to cancer and metastatic progression and TMEM16A inhibitors have anti-cancer properties. We are using structural and biochemical approaches to understand how TMEM16 proteins work and how drugs bind and modulate their activity. Ultimately, our objective is to establish these as novel therapeutical targets against cancer.
PM: What would you say is the most exciting finding in your field which helps to shape your research?
CP: This is a really exciting time to be a structural biologist. The recent emergence of cryo-EM as a robust method for determining high-resolution structures of proteins without the need for crystallization has revolutionized many fields of biology. This is particularly true for membrane protein biology, which are notoriously recalcitrant to crystallization. In the last few years, an unprecedented number of first-in-class structures of membrane proteins have been solved and the field is now quickly moving towards exploring the conformational landscape of these proteins in a near-native environment to understand how different stimuli and drugs induce different states and regulate their activity.
PM: The most controversial question in your field right now?
CP: The TMEM16 family comprises 10 closely related paralogs. Despite their similarity in sequence, the functional diversity of this family of membrane proteins is astonishing. For instance, some members function as ion channels, whereas others serve as lipid scramblases and some present dual functionalities. How structurally similar organizations mediate such diverse functionalities and what mechanisms underlie these activities is not understood. Different groups have proposed conflicting models for activity and even the interpretation of recently published structures and what state of the cycle they might represent remains debated. Through my postdoctoral work, I hope to answer some of these fundamental questions.
PM: How your activities demonstrate your leadership and sphere of influence at the institutional level and beyond. And the impact and importance of those activities in terms of your career aspirations.
CP: As a graduate student at The Scripps Research Institute, I was a member of the Graduate Student Council, a student-lead organization that advocates for student well-being. As the Chair of the Committee against sexual harassment, I lead our efforts to make Scripps compliant with Title IX regulations, ensuring that everyone on campus got access to important resources to deal with such situations. More recently, I was elected Chair of the 3D electron microscopy Gordon Research Seminar (GRS) to be held on 2021 in Sunday River, Maine. Here,I aim to create a welcoming environment that will serve as a forum for graduate students and postdocs to present and discuss their research with the community.Organizing this meeting also provides a unique networking opportunity for me,as I will be working closely with our attendees, session chairs, invited speakers, as well as our contributors.
PM: What are your major interests outside the lab?
CP: I love playing board games as well as outdoor activities. My main hobbies are camping,hiking, skiing, beach volleyball and snorkeling. Since moving to SF, I have started climbing, but this is still a work in progress.
PM: What is the one piece of advice you could give to someone considering a research career?
CP: The most important advice I would give to anyone starting a research career is to choose a good mentor over any scientific project. No matter how much you love a scientific question, you will end up hating it if you are miserable in lab due to a bad environment or mentor. In my experience, you can become passionate about any biological system and/or technique when you are in a good environment that makes you happy to go to work every morning and learn something new everyday. While publications are of course very important, a mentor that genuinely wants you to succeed and will later promote you for positions and write you a good recommendation letter is equally, if not more, important.
PM: Thank you for taking the time to discuss your research, Dr. Puchades! We wish you the best of luck!