Autophagy researchers

Nadezda Apostolova

Email: nadezda.apostolova@uv.es

Research focus

Molecular and cellular mechanisms responsible for the hepatic and metabolic adverse effects associated with the antiretroviral drugs employed to treat HIV-1 infection.

Model system

Human hepatic cells, both primary culture and hepatoma cell lines.

Education and career

2001, biology degree, specialty in biochemistry and physiology, Faculty of Natural Sciences and Mathematics, “St. Cyril and Methodius” University, Skopje, Macedonia. 2005, MSci, University of Valencia, Valencia, Spain. 2008, PhD in pharmacology, University of Valencia. 2008–2011, postdoctoral investigator at CIBERehd (National Network of Biomedical Research into hepatic and digestive diseases), Valencia, Spain. 2011–present, researcher at the Department of Pharmacology, Faculty of Medicine, University of Valencia, currently funded by the “Juan de la Cierva” postdoctoral research program of the Spanish Ministry of Science.

Why do you study autophagy?

Autophagy is a fascinating cellular adaptation process that goes far beyond the mere “recycling” of cellular compartments. Our research group explores the involvement of this process in the adverse effects associated with antiretroviral therapy, in particular the metabolic and hepatic toxicity produced by anti-HIV-1 drugs. We have recently described a novel mechanism of mitochondrial dysfunction related to these drugs, in particular with Efavirenz, a non-nucleoside reverse transcriptase inhibitor which is the cornerstone of the current antiretroviral combination regimes. Of note, clinically relevant concentrations of EFV induce autophagy in cultured hepatic cells promoting cell survival; however, exceeding a certain threshold of mitochondrial dysfunction is associated with an autophagic stress or blockage of the autophagic process. We are beginning to understand the role that autophagy plays in different pharmacological settings and, specifically, the interaction that takes place between autophagy and other stress response programs in the mammalian cell. Of a particular interest is the interconnection between autophagy and apoptotic cell death. In this regard, we think that the findings we have obtained so far and future results may have important therapeutic potential.

What do you hope to achieve in your scientific career?

Being able to understand a cellular process in its integrity requires many years of patience, hard work and creative research. I hope to be able to reach that point in a scientific career when one feels that one truly understands a process, and also very importantly, to be able to transmit this knowledge properly to the scientific community. I also consider it essential to be able to describe one’s field of research simply but accurately to the wider general public in the form of divulgatory or popular science. I think that all these are extraordinary achievements.

If you could start over and choose a different career, what would it be?

I am very fond of traveling, particularly when it brings me close to nature and wilderness. Visiting the Peruvian jungle, the Mongolian steppe and the Arctic have all had a major impact on my life and outlook. In fact, I avoid watching travel programs on TV, as knowing about all the beautiful places I have yet to see (or, perhaps, never will) puts me in a bad mood! If I were not a scientist I would love to spend my time traveling as a nature photographer, though this is more like a romantic dream. Research has always been my passion and what I wanted to do since I was a child. Still, traveling and photography are now my hobbies.

Personal comments

I was born in the Republic of Macedonia (then part of Yugoslavia). When I finished my degree, it was common for Macedonian graduates wanting a career in science to do a PhD abroad, and in my case it turned out to be Spain. Due to personal and professional preferences, many of us remain working abroad. I have lived in Spain for 10 years now and speak fluent Spanish, and though I like living here for many reasons, I still feel Macedonian.

Ana Coto-Montes

Email: acoto@uniovi.es

Research focus

Aging, in a very wide sense.

Model system

In general, we work with organisms and not with cells in culture. We focus on the Harderian gland of Syrian hamsters as an oxidative and autophagic animal model; on muscular tissue from aged humans to find a marker of fragility; and, on muscular tissue from cows after sacrifice to find a marker of tenderness.

Education and career

1995, PhD in biology, Cellular Biology Department, University of Oviedo, Oviedo, Spain; advisors: Dr. Delio Tolivia and Dr. Armando Pelaez. 1995–1996, first postdoctoral position in cancer research, University of Cantabria, Spain; advisor: Dr. Emilio Sánchez-Barceló. 1996–1998, second postdoctoral position in oxidative stress research in unicellular organisms, University of Göttingen, Germany; advisor: Dr. Ruediger Hardeland. 1999–2006, senior research fellow and “Cellular Response to Oxidative Stress (cROS)” Group leader, University of Oviedo. 2006–present, professor of morphology and cellular biology, University of Oviedo, and cROS leader.

Why do you study autophagy?

After finishing my “Marie Curie” postdoctoral position in the University of Göttingen in 1998 and before returning to Spain, I spent a couple of months in the Cellular Biology Department in Göttingen University with Dr. Robinson as advisor. At that moment he was studying autophagy in plant cells and I was learning several methodological procedures with him using his biological material. Once in Spain I continued with my doctoral research on oxidative stress in the harderian gland. One day, I was reviewing my old thesis microphotographs when I clearly saw structures similar to those present in Dr. Hillmer’s samples (Stefan Hillmer worked on autophagy with Drs. Yuji Moriyasu and David Robinson). I was amazed!!! They were autophagosomes. From that moment, autophagy has been the answer to countless questions in my research field.

What do you think is a key question in the autophagy field?

Finding a clear marker that allows distinguishing, at early phases, between survival that is dependent upon autophagy, and cell death by autophagy. At least in our research this would be an important goal.

Is teaching a substantial part of your current position? If so, what do you teach?

As a faculty member at the University of Oviedo, I spend a significant amount of my time on preparing lectures and classroom teaching. My position as a cell biology teacher allows me to update, year after year, my knowledge about cellular structure and function, which is very important in the autophagy field.

Personal comments

Outside of the lab, I am married to another scientist and we have two children, therefore we have just a scarce amount of free time, and most of this time we spend talking about his or my science field. But when science is put aside, we love traveling—any place, which lets us disconnect from our routine, is a favorite destination.

Wei-Pang Huang

Email: wphuang@ntu.edu.tw

Research focus

Molecular mechanisms underlying selective autophagy pathways.

Model system

The yeast Saccharomyces cerevisiae and mammalian cells.

Education and career

1997–2002, PhD in cell and developmental biology graduate program, University of California, Davis, CA, USA; advisor: Dr. Daniel Klionsky. 2002–2003, postdoctoral associate, University of Michigan, Ann Arbor, MI, USA; advisor: Dr. Daniel Klionsky. 2003–2007, assistant professor, Department of Life Science, National Taiwan University, Taipei, Taiwan. 2007–2012, associate professor, Department of Life Science, National Taiwan University. 2012–present, professor, Department of Life Science, National Taiwan University.

Why do you study autophagy?

Ever since I was an undergraduate student, I was fascinated by the beauty of the world of cells. I think the seeds for this interest were sown by Professor Chia-Chyuan Chen, who showed us such beautiful EM pictures in a cell biology course. After graduation, I joined his laboratory to study mouse acrosome formation mostly using EM-related techniques. Two years later, I received my master's degree, with a semi-satisfied mind. On the one hand, I became interested in the membrane trafficking field, but on the other hand I was frustrated by pure morphological research strategies at that time. As a consequence, I decided to pursue a doctoral degree and acquaint myself with genetic and molecular biology experimental methods. Joining professor Dan Klionsky’s laboratory, then at UC Davis, was my first choice after rotations, and since then I have been working on autophagy regulation.

What do you think is a key question in the autophagy field?

How selective cargoes elicit signals to stimulate autophagy activity.

Is teaching a substantial part of your current position?

There is a tendency in our institution that junior faculty members have more courses to teach. I used to teach 17 hours per week on average when I was an assistant professor. Although it took a significant amount of my time to prepare the materials and actually teach in classrooms, I kind of enjoyed it because the responses I received from students relieved my stress a lot. Twice, I received University Teaching Awards before I received a promotion to associate professor. Even now, I still have to share teaching general biology, cell biology, cell biology laboratory, histology, histology laboratory, and departmental seminar courses with other faculty members. Unfortunately, teaching is considered a basic requirement of our job, yet it does not count much when we are evaluated for promotion.

Personal comments

English is my second language. Other than textbooks and scientific articles, I didn’t read English books until Dan Klionsky introduced me to several sci-fi and fantasy novels, such as Dune and The Lord of the Rings. I managed to find time to read those books while I was studying for my degree. After I came back to my home country to become a teacher, most of my time was occupied by work-related activities. I seldom have opportunities to read English novels. Then, my daughter was born about two years ago. While I enjoy the time playing with my daughter for now, I hope someday I will sit opposite my daughter at a desk reading books that we like.

Jon D. Lane

Email: jon.lane@bristol.ac.uk

Research focus

Molecular regulation of autophagosome biogenesis.

Model system

Human cell-lines and primary human cells including erythroid progenitors.

Education and career

1991, BSc (honors) in biology, University of Southampton, Southampton, United Kingdom. 1995, PhD, University of Exeter, South West England, UK; advisor: Howard Stebbings. 1995–2002, postdoctoral researcher, University of Manchester, Manchester, UK; advisors: Viki Allan and Philip Woodman (worked on microtubule motors and membrane trafficking in viable and apoptotic cells). 2003–2007, Wellcome Trust Career Development Fellow, School of Biochemistry, University of Bristol, Bristol, UK. 2007–2012, Research Councils UK Senior Research Fellow, University of Bristol. 2012-present, Reader in Cell Biology, University of Bristol.

Why do you study autophagy?

Simply put, I think that autophagy is the most exciting field in cell biology at the current time. What could be better for a cell biologist than having the opportunity to study how cells assemble membrane organelles from scratch, using a dedicated set of novel molecules? From the perspective of membrane dynamics and trafficking, membrane/cytoskeletal interactions, and cellular function in health, differentiation and disease, there is no better field to be in. The turning point for me was the joint Keystone meeting on “Apoptotic and non-apoptotic cell death pathways” and “Autophagy in Health and Disease,” held in Monterey in 2007, which my group attended to present our work on membrane trafficking in apoptosis and our new story about caspase cleavage of ATG4D. This meeting was memorable because the autophagy sessions were incredibly exciting, whereas the cell death sessions were less so—I knew at that point that I had to dedicate my research to this emerging field.

What do you think is a key question(s) in the autophagy field?

There are still so many questions to answer about the basic mechanistic control of early autophagosome assembly—the question of where the autophagosomal membrane originates from remains to be completely resolved, for example. There are also many gaps in our understanding of how membrane flux through the autophagy system has an impact upon other membrane trafficking pathways within the cell, and the overall effect this has on cell function and viability.

What do you hope to achieve in your scientific career?

That’s a very tricky question to answer. To give a balanced response, I would say that I would like to make a significant impact in my chosen field—to identify new and fundamental molecular mechanisms, and to contribute to the overall understanding of cellular processes. I do hope that my research will have a wider impact toward a better understanding of human disease. Whether this comes directly from my research or indirectly via the training that I constantly provide for the next generations of young scientists matters rather less.

Is there a key experiment/finding that stands out in your mind with regard to autophagy?

I would highlight the seminal work from Ohsumi’s lab showing that Atg12 and later Atg8 act as ubiquitin-like protein and lipid modifiers, respectively. Although perhaps it might not be argued that this work was responsible for triggering the huge, broad interest in autophagy that has come about from subsequent studies of its impact on human disease, these papers elegantly demonstrate how autophagosomal membrane dynamics are regulated at the molecular level, and how unique the autophagosome assembly pathway truly is.

If you could meet any scientist, currently living or from the past, who would it be and why?

Ernst Abbe—an inspirational microscopist and scientific thinker. I would like to ask him his opinion of the recent super-resolution optical advances, and would be interested to know how he could better these methodologies.

If you could start over and choose a different career, what would it be?

Do I have to choose a different career? I like this one!

What one scientific discovery do you wish you had made?

There’s little doubt that GFP has revolutionized cell biology, so to have been involved in its discovery and early functional application would have been marvelous.

Is teaching a substantial part of your current position? If so, what do you teach. Does it benefit your research, or benefit from your research?

I do a reasonable amount of undergraduate and postgraduate teaching, and have the pleasure to teach autophagy to final year undergraduates in our biochemistry program. This experience has shown me that teaching can have a massive positive impact on your own research—to understand things to the level that you are able to teach them can be a huge benefit when putting your own findings into context. The ability to communicate your research clearly and enthusiastically is a crucial skill for all scientists, regardless of who the audience is, and I think that we have an obligation to be able to explain what we do and to share our enthusiasm with colleagues, with students and with the general public alike.

Personal comments

Outside the lab, my life centers on my family and in particular my beautiful daughters (8 and 5 years old). I also have to admit that I do spend a disproportionate amount of time watching/listening/worrying about my favorite football team—West Bromwich Albion—and also love spending time on the golf course (I just wish my golf balls did the same). As for authors, I particularly enjoy Evelyn Waugh, Steinbeck, Hemingway, Joyce and Murakami, and think that the finest film ever made was “Jaws,” although nobody ever seems to agree with me on that one…