Autophagy researchers

Nadine Camougrand

Email: n.camougrand@ibgc.cnrs.fr

Research focus

Mitophagy, quality control of mitochondria.

Model system

Yeast, Saccharomyces cerevisiae.

Education and career

1979, MD, University of Bordeaux (Bordeaux 2), Bordeaux, France. 1983, thesis at Bordeaux 2 University; advisor: Dr. Martine Guerin. 1987, PhD, University of Bordeaux 2; advisor: Dr. Martine Guerin. 1983–present, junior then senior researcher in CNRS, Institute of Cellular Biochemistry and Genetic, UMR5095, CNRS and Victor Segalen University, Bordeaux, France.

Why do you study autophagy?

Since the beginning of my scientific career, I have taken an interest in studying mitochondria metabolism, using yeast as a model system. At the beginning of 2000, we were working on one of the proteins of the “SUN family,” the Uth1 protein. We discovered that the mutant strain deficient for this protein was more resistant to rapamycin and nitrogen starvation than the parental strain and it was the beginning of our story with autophagy and mitophagy. In yeast, it is possible to correlate metabolism, in regard to mitochondrial function, with the carbon source added in the growth medium. On glucose, yeast obtains energy by fermentation, and the Crabtree effect prevents the differentiation of fully functional mitochondria. However, on a respiratory carbon source (lactate or glycerol/ethanol) mitochondrial respiration is essential for growth and viability, and mitochondrial biogenesis is vigorous; as a result, cells contain a high number of optimally differentiated mitochondria. Thus, getting rid of mitochondria during growth in glucose and in a respiratory carbon source may have to involve distinct mechanisms, and may also have diverse consequences for the cells. Indeed, the use of a respiratory carbon source has permitted us to visualize mitophagy in yeast, and these conditions have also permitted other groups to realize genetic screens that have identified molecular players such as the mitochondrial receptor Atg32. Now we are interested in the physiological role of mitophagy knowing that mitochondria play an important role in various processes that are essential for cell life. We have recently found that some mitophagy components combined with an increase in the reduction of cytochrome b (a component of the respiratory chain complex III) play a regulatory role in the induction of autophagy.

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

Yeast is a unicellular eukaryotic organism whose cells divide during culture and it is not necessary to eliminate some scarcely damaged mitochondria. When yeast cells reach the stationary phase of growth, their environment is similar to starvation conditions and they have accumulated nonfunctional molecules with age. In these conditions, induction of mitophagy could be relevant. The complexity of multicellular eukaryotic organisms leads to more difficulties in studying mitophagy, reinforced by the fact that cells are mitotic or postmitotic with different attributes. Investigations will be necessary to improve our understanding of the various physiological roles of mitophagy, but also to unearth all mysteries of mitophagy not yet addressed in particular in human cells, because of the involvement of mitochondria in numerous diseases.

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

There are two wonderful scientists who have received a Nobel Prize, Peter Mitchel (for his contribution to an understanding of the biological energy transfer through the formulation of the chemiosmotic theory that has permitted the understanding the actual process of mitochondrial oxidative phosphorylation) and Christian de Duve (the pioneer of autophagy) that I would like to meet because of their great contributions, and to ask them how they would see the outlook of their research in the long term and the impact of their discoveries, how they would consider the current competition among scientists and the race to publish, and how quickly knowledge has evolved.

Personal comments

I grew up on a farm, and now it is important for me to reestablish contact with the countryside sometimes. In my free time I love hiking in places like the rocky coastline of Bretagne (west of France) or in the Pyrénées mountains, as well as in the Aubrac plateau. And it is a real pleasure to immerse yourself in such an atmosphere with flowers, animals, colors and magic landscapes…I also love to spend time with my family (I have two children and both of my parents are living) and with friends. It is also necessary for me to read (I enjoy all kinds of novels—adventure, historical, science fiction, detective), cook (I like to try new French recipes) and to do some gardening.

Gerry McInerney

Email: gerald.mcinerney@ki.se

Research focus

Cellular responses to viral infection.

Model system

Semliki Forest virus infection of various permissive cell lines from human and mouse.

Education and career

1994, BSc (Hons) microbiology, University College Dublin, Ireland. 2000, PhD in Molecular Virology, Institute for Animal Health and University of Reading, UK; advisors: Drs. Andrew King and Graham Belsham. 2000–2005, postdoctoral researcher, Karolinska Institutet, Sweden; advisor: Prof. Peter Liljeström. 2008–2013, senior scientist and group leader, Department of Microbiology, Tumour and Cell Biology, Karolinska Institutet. 2013–present, associate professor, Department of Microbiology, Tumour and Cell Biology.

Why do you study autophagy?

I am interested in all aspects of cellular responses to virus infection, particularly the type I interferon response and EIF2AK2/PKR-dependent translation inhibition via the assembly of RNA stress granules. Autophagy has several connections with these pathways, and there may be more still to be described. I came rather late into the field, when it was already shown that several RNA viruses are inducing the accumulation of autophagosomes in the cytoplasm of infected cells, but in many cases, the causes and consequences of this for the outcome of infection are unclear.

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

I think a lot is still to be described about autophagy in virus-infected cells. The pathway appears to promote viral replication in some contexts, but may represent part of the cellular antiviral defense in others. Much greater understanding is required if we are to develop, for example, pharmacological agents targeting this pathway to treat viral infections. I hope my work can contribute in some way to this.

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

As a student I was a big fan of the books and essays of Stephen Jay Gould. I still am, but I notice that he wrote very little about evolutionary processes among viruses. To me, the ability of viruses to rapidly adapt to new conditions is a great example for the teaching of evolution by means of natural selection. It may have been interesting to hear his take on the subject.

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 have been involved in teaching at various levels at the Karolinska Institutet since I joined as a postdoc, but I have recently taken up responsibility for the teaching of virology for the biomedical science course. It has been a privilege to implement changes to the lecture and laboratory schedules according to my view of the subject.

I also organize a very popular research summer school for high school students at the Institute. This consists of two weeks of lectures and four weeks of laboratory work in an active research group. Application is open to all Swedish high schools and competition for places is high—the hardest part of the job is choosing only 20 students from the many applications.

There is little doubt in my mind that teaching and research are mutually beneficial. It is generally accepted that students are more likely to be inspired by teachers who are also engaged in research, and this promotes “higher-order” learning. As a teacher, the benefits are numerous. I have the advantage of seeing the subjects from a different perspective during the preparation of my lectures and laboratory demonstrations. Also, undergraduate courses are a great hunting ground for recruiting talented PhD students.

Personal comments

Establishing an independent research group as well as expanding my teaching has not left much time for other interests in recent years. I’m lucky to have a number of good friends in Sweden, the UK and Ireland who I try to see as often as possible. For exercise, I try to run as often as I can in the many beautiful parks and trails around Stockholm. I’m not a very strong runner, but I’m hoping in 2013, the year of my 40th birthday, to beat my personal best time in the Stockholm half marathon. I realize this sounds very much like a mid-life crisis, and I’m fine with that.

Rubem F.S. Menna-Barreto

Email: rubemb@ioc.fiocruz.br

Research focus

Autophagy in pathogenic protozoa and the biological relevance of this process during the infection of mammalian cells.

Model system

Pathogenic protozoa Trypanosoma cruzi, Leishmania sp. and Toxoplasma gondii, and different primary culture cells.

Education and career

2003, biological sciences degree, University Santa Ursula, Rio de Janeiro, Brazil; advisor: Solange Lisboa de Castro. 2008, PhD in cellular and molecular biology, Oswaldo Cruz Foundation (FIOCRUZ), Rio de Janeiro, Brazil; advisors: Solange Lisboa de Castro and Maurilio José Soares. 2009–2010, postdoctoral researcher in T. cruzi mitochondrial bioenergetics, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil; advisor: Marcus Fernandes Oliveira. 2008–present, associated researcher in the Cell Biology Lab at FIOCRUZ.

Why do you study autophagy?

Autophagy is an essential pathway involved in crucial cellular events such as differentiation, and the turnover of macromolecules and/or organelles. In the Trypanosomatidae and Apicomplexa protozoa model, it has been demonstrated that the autophagic process is involved in the interaction between parasites and host cells, being decisive for the success of infection. These pathogens represent serious economic and health problems especially in developing countries, and the available chemotherapy for those diseases is very limited. The medical relevance of these parasites associated with the previously described participation of autophagy in the pathogen-host cell interaction, stimulates us to further investigate the possible molecular regulation processes involved. I have extensive experience in electron microscopy, performing this technique as a gold standard method in all of our models to characterize autophagic features.

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

The exact mechanism involved in the autophagic balance/misbalance, leading to cell survival or death, is an exciting question. Another interesting point is the regulation process associated with the selection of the particular kind of autophagy that will happen. For example, why some structures are degraded by macroautophagy versus microautophagy depends on the specific situation. Also, why does the phagophore originate from the endoplasmic reticulum in some cases and from the Golgi and/or other membranes in other cases?

Why is the field of autophagy important to you?

The regulation events responsible for selection of the type of autophagy that will occur certainly influence the cell phenotype, resulting in consequences for the whole organism. For diseases associated with protozoa, for example, it is important to understand the regulation of autophagy as a potential therapeutic target, allowing us ultimately to use this process to induce cell death as a mechanism to fight infection.

What do you hope to achieve in your scientific career?

Recently, my small research group was established, and I hope to increase my contributions in the autophagy field in the next few years. I would like to describe the physiological role of the autophagic selection outcome in different models.

Which paper in your research field represents seminal work on autophagy?

It is hard to choose only one paper. The one by Mizushima and colleagues (1998) where they describe the Atg12–Atg5 complex, and two papers of De Duve’s group (1967) showing that autophagy is induced by glucagon, are landmarks for me.

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

I would really appreciate meeting Christian de Duve due to all his crucial findings about autophagy and lysosomes.

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

I couldn’t imagine being in any other career in which I would be as completely fulfilled as a scientific career. I really love the constant challenge with the unknown. Having said that, I like very much music and photography, too.

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?

Unfortunately, my institution is not a university, but is a research center, which is the reason we don’t have graduate courses. However, there are six different PhD programs in my institute, and I am always teaching. Nowadays, I coordinate two disciplines in the cellular and molecular biology program, one of them being about the physiology of cell death, where I try to show the complex balance between homeostasis and death, including autophagy. I also contribute as an invited teacher in many other disciplines, teaching essentially about parasitology, cell biology, mitochondria and microscopy. Recently, we have been organizing short courses (one or two weeks) for undergraduate students about relevant medical topics every summer and winter. Last winter, we organized a course named “Autophagy: from homeostasis to death” in order to spread the knowledge about autophagy among young students. It was a really exciting experience and I hope to repeat it.

Personal comments

Outside the lab, I really enjoy travel a lot to learn more about different cultures, especially ancient civilizations, such as in Greece, Italy and Peru, wonderful places that I visited and recommend to others. In my free time, I also read romances, run to keep in shape and play electric guitar in my rock n’ roll band (named Lynx, from the constellation in the northern sky) to prevent scientific-related stress. As a microscopist, it is not a surprise that I love photography. On weekends, I spend a lot of time taking pictures of landscapes, and macrophotography of insects and flowers is another passion. I am a single (and simple) guy, very curious and proactive, these last two I think being essential characteristics to make a good scientist.

Tassula Proikas-Cezanne

Email: tassula.proikas-cezanne@uni-tuebingen.de

Research focus

Autophagy, cancer, aging.

Model systems

Mammalian cells in culture, Caenorhabditis elegans.

Education and career

1995, PhD (Dr. rer. nat.), University of Hamburg (external thesis in the laboratory of Dr. Silvia Stabel at the Max Planck Institute, Cologne), Germany. 1995–1999, postdoctoral scientist, Marie Curie Research Institute, Oxted, UK; advisor: Dr. John R. Jenkins. 2000–2002, postdoctoral scientist, Temple University, Philadelphia, PA, USA; advisor: Dr. John R. Jenkins. 2003, research scientist, Interfaculty Institute of Cell Biology, Eberhard Karls University, Tuebingen, Germany. 2004–present, independent group leader, Interfaculty Institute of Cell Biology, Eberhard Karls University. 2012, habilitation in Molecular and Cell Biology. 2012–present, faculty member of the International Max Planck Research School, Tuebingen.

Why do you study autophagy?

The process of autophagy holds essential, yet undiscovered secrets of eukaryotic life, such as the molecular connection between aging and tumor development. Recently, substantial advances have been made in this field and it is a very exciting time to consider autophagy and its implications for life and health. It is a great honor and joy to be part of this groundbreaking research community.

How did you get into the autophagy field?

By screening for novel TP53/p53 inhibitory factors during my postdoctoral research period in the UK, I isolated a partial cDNA encoding human WIPI1 and found that the sequence belonged to a novel human gene and protein family, which I later cloned in Tuebingen. Looking into homologous sequences it became apparent that yeast Atg18 should represent an ancestral version of human WIPI. Due to this, I became interested in autophagy, founding my research group with the goal to further investigate the roles of human WIPI proteins in autophagy. Indeed, we found that WIPI1 and WIPI2 have essential functions as PtdIns3P effectors during the initiation of autophagy and further become membrane proteins of early autophagosomes. Now, we work on defining the roles of the different WIPI proteins in autophagy, with particular focus on autophagic events during tumor development.

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

An important question in this field is how the early autophagic membrane rearrangements occur and what the implications of these are for autophagosome formation and lysosomal communication. We still do not fully understand how autophagosomes are formed, or how they communicate with the lysosomal compartment under different circumstances. Further investigation into these areas should, in the near future, provide rational therapeutic strategies to target altered autophagic activites and capacities in human pathologies such as cancer.

Is teaching a substantial part of your current position?

Very much so. Initially, I held some lectures and practical courses for advanced biology and biochemistry students, but during the last years this evolved substantially and each semester I am now teaching up to 500 students from the fields of medicine, biology, biochemistry and bioinformatics. My biggest teaching commitment is a practical course for 300–400 first semester students, in which I infused both content and structure with the active-learning approach on the topic of autophagy. My students conduct WIPI1 puncta-formation analysis by fluorescence microscopy in their first week of university, which is always well received. It is my strong belief that students greatly benefit from lectures and courses that are close to interesting current research topics, such as autophagy. I further think it is important to consider the view of students new to these fields, questioning textbook facts and indicating room for experimental and hypothetical improvements.

Personal comments

I truly enjoy my life in science and do wake up every morning in eager anticipation of new results in the lab. Outside of science, I also love the opera, Picasso, hiking in the Alps, Greek music and my daughter, in reverse order, of course.