Fu-Cheng Lin
Email: fuchenglin@zju.edu.cn
Research focus
The role of autophagy in the virulence of pathogenic fungi.
Model system
The rice blast fungus, Magnaporthe oryzae.
Education and career
1990, MD, plant pathology, Zhejiang University, Hangzhou, China; advisor: Prof Qi-Xin Ge; 1998, PhD, plant pathology, Zhejiang University; advisor: Prof De-Bao Li; 1999–2001, visiting scientist, School of Biological Sciences, University of Exeter, Devon, UK; advisor: Prof Nicholas J Talbot; 2003–present, professor, Department of Plant Pathology, Biotechnology Institute, College of Agriculture and Biotechnology, Zhejiang University.
Why do you study autophagy?
Magnaporthe oryzae infects its host by forming a specialized infection structure, an appressorium, on the rice leaf. Enormous appressorium turgor is the key factor to penetrate the host successfully. In my group, we found that autophagy is necessary for the formation of the conidium and its appressorium, and for normal development and full pathogenicity of M. oryzae. Subsequently, we have analyzed protein components and their interactions in the autophagy pathway in M. oryzae related to appressorial morphogenesis and the establishment of turgor. Autophagy is a fascinating field of study with regard to the plant pathogens, and we use the plant pathogenic fungus M. oryzae as a model.
What do you think is a key question in the autophagy field?
How autophagy influences the turnover of materials to form the appressoria is the key question in the area of autophagy with regard to Magnaporthe.
Why is the field of autophagy important to you?
Clarification of the functions and network of interactions among the proteins expressed by the M. oryzae autophagy genes will lead to a better understanding of the role of autophagy in fungal pathogenesis and help in the development of new strategies for disease control.
What do you hope to achieve in your scientific career?
A key goal that stands out in my mind is focused on distinguishing the main components in the molecular machinery of autophagy among pathogenic fungi, and trying to identify and/or design certain chemicals targeting those “points” to block the autophagy pathway and thus lead to the loss of virulence of pathogenic fungi.
Currently, I wish to sort out the regulation mechanism of the MoATG1 complex. I find this to be intriguing with regard to the initiation of autophagy, since it both accepts signals from upstream and transfers these signal to downstream components. We are now trying to crystallize several protein components and learn how they interact into each other in vivo.
Which paper from your lab represents seminal work on autophagy?
Liu XH, Lu JP, Dong B, Zhang L, Min H, Lin FC. Involvement of a Magnaporthe grisea serine/threonine kinase, MgATG1, in appressorium turgor and pathogenesis. Eukaryotic Cell 2007; 6: 997–1005.
If you could start over and choose a different career, what would it be?
It would be a career as an architectural designer—my childhood dream was to design a gorgeous house for mum and dad, and my family, and many buildings for people throughout the world. Now, I could imagine selecting and imitating the structure of a cell, or an autophagic body, or even a fusion complex between autophagosomes and an individual vacuole under the microscope, and then figure out a structure for the design of a novel, man-made building—that would be something indeed!
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?
As a professor at Zhejiang University, I have a token task to teach undergraduate students and graduate students in the molecular biology of fungi since the year 2001. Talking to the students about our novel research results and the knowledge presented in newly published articles can fascinate students and lead them to form their own specific aims. Sharing current scientific knowledge definitely promotes an effective level of teaching! Meanwhile, exchanging some different and fresh ideas with students also stimulates my own thinking.
Personal comments
In my free time, I particularly like to swim and listen to some classical music, and I enjoy reading several books written by Chinese ancient philosophers (not all at the same time).
Dalibor Mijaljica
Email: Dalibor.Mijaljica@monash.edu
Research focus
“Organellophagy” in yeast with a focus on nucleophagy and mitophagy.
Model system
Saccharomyces cerevisiae.
Education and career
2001, BSc, Department of Biochemistry and Molecular Biology, Monash University, Melbourne, Australia. 2002, BSc (Hons), Department of Biochemistry and Molecular Biology, Monash University; advisors: Prof Rod Devenish and Dr Mark Prescott. 2003–2009, PhD, Department of Biochemistry and Molecular Biology, Monash University; advisors: Prof Rod Devenish and Dr Mark Prescott. 2009–2011, postdoctoral research fellow, Department of Biochemistry and Molecular Biology, Monash University; advisor: Prof Rod Devenish. 2012, teaching associate, Department of Biochemistry and Molecular Biology, Monash University; advisor: Prof Lynne Mayne. 2013–present, technology development researcher, Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University; advisors: Dr Michelle Halls and Dr Meritxell Canals.
Why do you study autophagy?
About a decade ago, as an undergraduate student, I became interested in organelles, fluorescent proteins, and fluorescence microscopy. Soon after, I joined Professor Devenish’s lab in the Department of Biochemistry and Molecular Biology at Monash and was working on improved fluorescent biosensors for monitoring autophagy in vivo. In collaboration with my colleagues, Dr Carlos Rosado, Dr Mark Prescott and Professor Rod Devenish, a fluorescent pH biosensor (“Rosella”) was developed as a tool to aid our studies of autophagy of organelles (“organellophagy”) in yeast, especially exploring the mechanism by which the nucleus or mitochondria are recognized and sequestered by their respective modes of autophagy, namely nucleophagy and mitophagy. During my postdoctoral training, I was working exclusively on nucleophagy and together with my advisors described the process of “late nucleophagy” in the yeast Saccharomyces cerevisiae, a mode of nucleophagy that is spatially and temporally distinct from other modes of nucleophagy described in this model organism to date. My ultimate goal is to further characterize the process of late nucleophagy in yeast as well as to extend these studies to mammalian cells by identifying major mechanistic players/regulators as well as determining the identity of different nuclear material/cargo, and the manner by which it enters the yeast vacuole/mammalian lysosomes under physiological, autophagy-induced, and pathological conditions.
What do you think is a key question in the autophagy field?
In the past decade, it has been established that cells use selective autophagy for a variety of purposes, including elimination of damaged, dysfunctional, and/or superfluous organelles as well as for remodeling to adapt to changing nutritional/environmental conditions. Accordingly, defects in both nonselective and selective autophagy are associated with a range of pathophysiologies in humans. Therefore, it is imperative to gain a deeper understanding of how both the adaptation of the core autophagic machinery and sophisticated mechanisms to recognize organelles destined for turnover through a diversity of nonselective and selective subtypes of autophagy play crucial roles in organelle homeostasis and quality control.
Which paper in your research field represents seminal work on autophagy?
For me, without a doubt the pioneering research performed by Professor David Goldfarb and colleagues on piecemeal microautophagy of the nucleus in Saccharomyces cerevisiae represents seminal work in the field of nucleophagy.
If you could meet any scientist, currently living or from the past, who would it be and why?
Nikola Tesla, an ordinary man in the course of time, yet a true revolutionary and visionary genius who lit the world. According to E Armstrong, “The world will wait a long time for Nikola Tesla’s equal in achievement and imagination.”
What one scientific discovery do you wish you had made?
I wish that I was involved in the discovery of at least one of the cellular organelles.
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?
Even though teaching is not a substantial part of my current position I was involved in several aspects of incorporating my research into a teaching course (cellular organization: organelle structure and function in health and disease) for third-year undergraduate students undertaking either a science or biomedical science degree at Monash. Together with my advisors I was involved in codesigning 2 laboratory-based practicals, focusing on visualizing organelles within yeast cells, developing PowerPoint presentations for syndicate sessions discussing “Rosella: a fluorescent pH-biosensor for reporting delivery of cytosol and organelles to the yeast vacuole for degradation” and “Autophagy of yeast organelles” as well as developing a scientific/educational video, “A fluorescence microscopy assay for monitoring mitophagy in the yeast Saccharomyces cerevisiae,” http://www.jove.com/video/2779/a-fluorescence-microscopy-assay-for-monitoring-mitophagy-yeast.
Personal comments
I was born in Croatia and grew up on the family farm close to the Adriatic Sea. Being surrounded by astonishing flora and fauna I developed a strong interest in plants and animals and my long-standing dream was to become a vet. I developed an interest in biology and science at an early age. Some of my favorite activities included collecting and preserving plant specimens (making herbaria) and all types of insects, digging up anthills and investigating their elaborate underworld cities. Furthermore, I am very familiar with the processes of winemaking and making olive oil. In 1997, I migrated to Australia and had to learn English from scratch. However, my love for biology and science was as strong as ever, and, soon after, I started my scientific journey in the field of autophagy. After all, there is at least a connection between winemaking and autophagy.
Sovan Sarkar
Email: sarkar@wi.mit.edu, sovan.sarkar@gmail.com
Research focus
MTOR-independent autophagy pathways and therapeutic application of chemical modulators in induced pluripotent stem cell-based disease models.
Model system
Mammalian cell lines, primary neurons, human embryonic stem cells, disease-relevant human cell-types derived from induced pluripotent stem cells.
Education and career
1997–2000, BSc, physiology, Presidency College, University of Calcutta, West Bengal, India. 2000–2002, MSc, biotechnology, School of Biotechnology, Madurai Kamaraj University, Tamil Nadu, India; advisor: Prof R Usha and Prof S Krishnaswamy. 2002–2006, PhD, medical genetics, Cambridge Institute for Medical Research, University of Cambridge, UK; advisor: Prof David Rubinsztein. 2006–2010, postdoctoral research associate, Cambridge Institute for Medical Research; advisor: Prof David Rubinsztein. 2007–2009, research fellow, Hughes Hall, University of Cambridge. 2010–present, postdoctoral associate, Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology, MA, USA; advisor: Prof Rudolf Jaenisch. 2010–present, former fellow, Hughes Hall, University of Cambridge.
Why do you study autophagy?
Among the basic cellular processes, autophagy is a strong contender that potentiates the unique opportunity to work at the interface of basic biology and therapeutic applications. The importance of autophagy lies in its implications in organismal physiology and diverse human diseases. Previously, I have identified the MTOR-independent autophagy pathways that are amenable to chemical perturbations. These findings are of greater clinical relevance as opposed to MTOR-dependent autophagy, since MTOR inhibitors can possibly have side effects pertaining to suppression of its critical cellular functions. Several MTOR-independent small molecule autophagy inducers discovered through our studies show protective effects in transgenic disease models, ranging from neurodegenerative disorders to liver diseases. I am currently studying autophagy alterations in disease-relevant human cells derived from patient-specific induced pluripotent stem cells. Combining the knowledge of autophagy dysfunction and the mechanism/efficacy of drug action may be rational for designing targeted therapy in disease-specific contexts.
What do you think is a key question(s) in the autophagy field, and where do you think the field is heading?
A key question from a fundamental perspective is the identification of specific autophagy substrates and their physiological roles; whereas from a biomedical perspective, it would be the discovery of a potent autophagy inducer specifically acting on the downstream machinery instead of the upstream signaling pathways. In the future, the field should witness clinical trials with autophagy modulators.
What do you hope to achieve in your scientific career?
I want to develop a pipeline originating with basic biology and going to drug discovery, and potentially translate the findings for biomedical applications. I wish to establish myself as a successful scientist with the goal of having an impact on human society through my research.
Is there a key experiment/finding that stands out in your mind with regard to autophagy?
Although the discovery of autophagy genes in yeast is of paramount importance, the identification of LC3-II, the specific autophagosome marker in mammals (Kabeya et al., EMBO Journal, 2000), initiated the exponential growth in this field by enabling researchers to study this process.
Which paper in your research field represents seminal work on autophagy?
In the field of autophagy and neurodegeneration, the paper by Ravikumar et al. (Nature Genetics, 2004) demonstrating the protective effects of autophagy induction in transgenic models of Huntington disease is a seminal work that stirred many subsequent studies of autophagy modulation in other diseases. In addition, the Hara et al. and Komatsu et al. papers (Nature, 2006) showing that deletion of essential autophagy genes in normal mouse brain caused neurodegeneration broadly implies that impairment of autophagy in neurodegenerative diseases may be a major contributing factor to the disease pathology.
If you could meet any scientist, currently living or from the past, who would it be and why?
I would like to meet various scientists from the past, traveling back in time and working with them during their notable discoveries, to understand how research was done and science was viewed back then, and to experience the life of a scientist—then and now.
If you could start over and choose a different career, what would it be?
I am passionate about the sport cricket, as well as travel and concept photography, and I could have gone professionally in either direction. However, I also have a desire to make movies, meaningful ones that convey social messages in developing countries, and so would have chosen a career path through film studies and the art of directing.
Personal comments
I believe life is fun so work hard to enjoy it. Being an avid traveler in various continents, I like to understand and capture the art, history and culture through my lenses. I like to understand what makes people different from varying socio-cultural backgrounds and how I can connect with them. On the same note, through my college life in Cambridge University, being a Gates Cambridge Scholar and later a research fellow at Hughes Hall, and now at MIT, I met several people from different parts of the world. Together with the global nature of science itself, these experiences make me feel a citizen of this whole world despite having Indian roots.
Teresa Zoladek
Email: teresa@ibb.waw.pl
Research focus
Protein traffic and its connection with actin cytoskeleton and ubiquitination.
Model system
The yeast Saccharomyces cerevisie.
Education and career
1979, master of pharmacy, specialization in clinical biochemistry, Warsaw Medical University, Poland. 1985, PhD, biological sciences, Institute of Biochemistry and Biophysics, Polish Academy of Sciences (IBB PAS), Warsaw, Poland; advisor: Prof A Putrament. 1985–1991, research assistant, IBB PAS, group of Prof Joanna Rytka. 1991–1994, postdoctoral fellow, Hershey Medical Center, Pennsylvania State University, Hershey, PA, USA; advisor: Prof Anita K Hopper. 1994–1999 assistant professor, Department of Genetics, IBB PAS. 1997–2004, instructor, molecular biology, Faculty of Pharmacy, Warsaw Medical University. 1999, Habilitation in Biology, IBB PAS. 1999–2005, associate professor, IBB PAS. 2005, professor of biology, IBB PAS. 2009–present, head, Department of Genetics, IBB PAS.
Why do you study autophagy?
I have a long-term interest in protein trafficking in the cell, especially its connection with actin cytoskeleton dynamics and Rsp5 ligase-dependent ubiquitination of proteins. In one of the screens for multicopy suppressors we found an ATG gene and this finding turned my focus to autophagy. I found the autophagy field to be very autophagy researchers very friendly and supportive. I was very excited to participate in the interesting and dynamic, and first Autophagy EMBO conference and have the opportunity to meet and discuss science with many of the attendees. My group is interested to know how ubiquitin ligases from the NEDD4 family are involved in autophagy.
What is a key question in the autophagy field?
There are still many questions to answer regarding the role of particular Atg proteins in autophagy. However, key questions are how substrates are selected for autophagic degradation and what is the mechanism of autophagy regulation in response to metabolic needs and environmental changes.
Is teaching a substantial part of your current position?
I was teaching molecular biology to pharmacy students for several years. I am not involved in teaching now. However, my lab is hosting bachelor’s and master’s degree students for their thesis work. I am passing my knowledge and enthusiasm for science to students and I am happy to see when some of them choose a scientific career.
Personal comments
I like to travel with my husband and sons to get to know the nature, culture, and people from other countries. My favorite sports are biking and skiing.