The Mokalled lab at Washington University School of Medicine is seeking outstanding applicants for multiple research positions (http://www.mokalledlab.com/). Our lab uses zebrafish and mouse model systems to study neural regeneration after spinal cord injury or disease. Candidates with enthusiasm for neuroscience, regenerative biology, and zebrafish research are encouraged to forward a cover letter, CV, and list of 3 or more references to mmokalled@wustl.edu.
The Waddington Medal is the only national Developmental Biology award in the UK. It honours outstanding research performance as well as services to the subject community. The medal is awarded annually at the BSDB Spring Meeting, where the recipient presents the Waddington Medal Lecture. Here we introduce the 2018 winner Richard Gardner who won the 2018 Waddington medal for his outstanding work in the field of early embryogenesis and stem cells, as well as continued contributions to the development of our field and the shaping of science policy in the UK.
Born in 1943, Richard Lavenham Gardner, Kt, MA, PhD, ScD, FIAT(Hon), FRSB, FRS studied at St. Catharine’s College and the University of Cambridge from 1963-1966, graduating with a First Class Honours B.A. in Physiology. For his PhD, he remained in Cambridge in the Physiological Laboratory of Robert Edwards (Nobel prize winner, pioneer in reproductive medicine and in vitro fertilisation / IVF), where he worked alongside Martin Johnson and was awarded his title in 1971 for his thesis entitled “Investigation of the mammalian blastocyst by microsurgery”. He stayed on in Edward’s lab as a research assistant for another three years, from where he moved to a University Lecturer position at the Department of Zoology, University of Oxford (1973-77). During that time (and beyond) he was a Visiting World Health Organization Fellow in Warsaw and Zagreb and Student of Christ Church (Oxford). In 1978 he became Henry Dale Research Professor of the Royal Society at the University of Oxford until 2003. Thereafter he held positions as Edward Penley Abraham Research Professor of the Royal Society (2003-8), honorary Visiting Professor at the University of York (2007-16), and is now an Associate at the University of Oxford and Emeritus Student of Christ Church, Oxford.
Scientifically, Richard is well known as a pioneer in the study of early mammalian development, having made many hugely important discoveries relating to the fate of cells in early mammalian development and the properties of stem cells derived from early embryos (see selected papers below). These were made possible by his strong knack for identifying important questions and addressing them in innovative and at the same time definitive ways, always with extremely elegant experimental design.
His numerous important scientific contributions include: being the first to use clonal analysis to fate map the early mouse embryo, along with experimental manipulations to assess the potency of individual cells, establishing how the germ line is segregated in the early embryo, and pioneering blastocyst injection for studying stem cell potency. His work laid essential foundations for pre-implantation genetic diagnosis, now widely used in human fertility clinics, and for the embryonic stem cell (ESC) field. He was one of the pioneers developing and using micromanipulation techniques in mammalian embryos, the kind of technique now commonly used, for example for human IVF and cloning (such as the cloning of the sheep Dolly). He is also known for his work on embryonic stem cell derivation (together with Frances Brook), demonstrating that ESCs originate from the epiblast and that the most efficient method to derive them in mouse is to use delayed-implanting blastocysts (diapause blastocyst).
The four surviving ICRF Developmental Biology Unit group leaders – Philip Ingham, David Ish Horowicz, Richard Gardner and Jonathan Slack at the BSDB Spring Meeting 2018.
Awards and Honours
Waddington Medal of the British Society of Developmental Biology (2018)
Patrick Steptoe Memorial Lecturer and medallist (2015)
Honorary Doctorate of Science from the University of Cambridge (2012)
Annual Lecturer Cumberland Lodge (2010)
Honorary Fellow, St. Catharine’s College, University of Cambridge, UK (2007)
Knight Batchelor in the Queens’ Birthday Honours (2005)
Albert Brachet Prize of the Belgian Royal Academy (2004)
Karl Beyer Visiting Professor, University of Wisconsin, Madison, WI, USA (2001)
Royal (Queen’s) Medal of the Royal Society (2001)
March of Dimes International Prize in Developmental Biology (1999)
Elected Fellow of the Royal Society of London (1979)
Scientific Medal of the Zoological Society of London (1977)
Belfield-Clarke Prize for the Biological Sciences (1966)
Elected Scholar of St. Catharine’s College (1966)
Kitchener Scholar (1963-66)
Prizes for Physics and Biology (1963)
First Prize in Natural History Essay (1959)
First Prize in Natural History Essay (1958)
Throughout his education and scientific career, Richard has excelled in outstanding performance, as is clearly demonstrated by the long list of awards and honours (see Box); and he has always been a committed member of the Developmental Biology community who contributed notably also in policy making relating to ethical issues connected with access and use of human embryos in research, ethical aspects of cloning, and ethical use of animals in research. His dedication is clearly reflected in the many important positions he served in throughout his career:
Editor of the journal Development (formerly J. Embryol. Exp. Morph, 1977-91) and editorial board member of the journals Gamete Research, Placenta and Cancer Surveys
President of the Institute of Animal Technology (1986-2006)
Independent Member of the Advisory Board for the Research Council (1989-93)
together with Walter Bodmer (head of ICRF) he co-founded the Cancer Research UK Developmental Biology Unit at Oxford’s Zoology Department (attracting the likes of Andy Copp, David Ish Horowitz, Jonathan Slack, Julian Lewis and Phil Ingham), of which he was Honorary Director (1986-96)
Vice President of the Zoological Society of London (1991-92)
Vice-President and Member of the Laboratory Animal Science Association Council (1996-99)
Trustee and then chair of the Edward Penley Abraham Research Fund (1999, 2003)
President of the Institute of Biology (now Royal Society of Biology; 2007- 08)
Chair of the Royal Society Working Group on Stem Cells and Therapeutic Cloning (1998-08)
Chair of the Animals in Science Education Trust (AS-ET; current)
Author of numerous reports to commissions, committees and inquiries of significant political impact
Organiser of various scientific conferences, meetings or discussion forums.
Richard’s enormous influence is also reflected in the fact that he was mentor to many illustrious embryologists, including Janet Rossant (PhD, 1976), Andrew Copp (DPhil, 1978), John Heath (DPhil, 1979), Paul Tesar (DPhil, 2007), Virginia E. Papaioannou (postdoc, 1973-81), Jenny Nichols (PhD, 1990), Karen Downs (1989-93) and the recipient of the 1999 Waddington medal Rosa Beddington (D. Phil., 1983) – to name but a few.
But it should also be pointed out that aside all this prolific work in science as well as science administration and policy, Richard still has been finding time for an impressive number of hobbies, of which he lists ornithology, music, sailing (unfortunately no longer!), gardening, clay shooting and painting landscapes in watercolour. To illustrate Richard’s continued dedication, he donated his latest three watercolour paintings to the AS-ET and they were sold for a gratifying £1150 to provide bursaries and other awards to enable laboratory animal technicians to advance their education and training.
The BSDB would like to congratulate Richard Gardner for the Waddington award, of which he certainly is a most worthy recipient.
An eclectic selection of some of Richard Gardner’s major landmarks publications:
Gardner, RL (1968) Mouse chimeras obtained by the injection of cells into the blastocyst. Nature 220: 596-7 — This paper describes the method of blastocyst injection in which small groups of donor cells derived from a genetically-distinct blastocyst are injected into the blastocoel cavity of a host blastocyst; chimeric blastocysts are then transferred to a foster mother and gestated to term. The paper also demonstrates that blastocyst cells contribute to the adult animal and germ line. The technique of blastocyst injection is still used routinely both to generate transgenic mouse models using genetically-modified embryonic stem cells.
Gardner RL, Lyon MF (1971)X chromosome inactivation studied by injection of a single cell into the mouse blastocyst. Nature 231: 385-6 — Using blastocyst injection of single inner cell mass (ICM) cells combined with genetic markers, this paper shows that the adult animal is derived from the ICM. It is also a landmark paper in the history of the discovery of X-inactivation.
Gardner RL, Papaioannou VE, Barton SC. (1973) Origin of the ectoplacental cone and secondary giant cells in mouse blastocysts reconstituted from isolated trophoblast and inner cell mass. J Embryol Exp Morphol. 30: 561-72 — In contrast to “blastocyst injection” (above) to determine the fate/potency of ICM cells via injection into the blastocoel cavity, the technique of “blastocyst reconstitution” was created to discover the fate and potency of the trophectoderm. The paper demonstrates that the trophectoderm gives rise to major components of the chorionic component of the placenta but not to the embryo proper. This allowed him to create the first fate maps of the mouse conceptus.
Gardner, RL (1982) Investigation of cell lineage and differentiation in the extraembryonic endoderm of the mouse embryo. J Embryol Exp Morphol. 68: 175-98 — At implantation, the ICM segregates into epiblast and primitive endoderm (PE). Using blastocyst injection, this paper shows that PE generates visceral and parietal endoderm, which are supporting tissues for the ICM-derived epiblast. This study expanded the mouse fate map to show that ICM gives rise to epiblast and primitive endoderm.
Acknowledgements: Andreas Prokop would like to thank Berenika Plusa for helpful information, Richard Gardner for sending information, images and approving the draft of this article, and Claudio Stern and Jonathan Slack for helpful information and thoughts taken from their nomination text.
This year, is the BSDB’s 70th anniversary! Expect many extras on our Spring Meeting (15-18 April 2018 in Warwick)! For example, the history rap, a contemporary oral rendering of BSDB history, featuring Jerry aka Gerald H Thomsen PhD and produced and mixed by Philip Larsen – BSDB member and DJ!
Here at Development towers the excitement is mounting for the BSDB’s Spring meeting, which starts in Warwick on Sunday. The meetings are always great fun but this year promises to be particularly special – the society is celebrating its 70th birthday and has assembled an all star cast of speakers.
The epic conference poster designed by Sally Lowell!
If you’re coming, be sure to check out The Company of Biologists’ stand and look out for Katherine Brown (Development Executive Editor), Seema Grewal (Development Reviews Editors) and Aidan Maartens (the Node Community Manager & Development Online Editor). We’ll also be accessible at the bar to talk about everything related to publishing, including preLights, the new preprints service.
As we looked at the line up we realised we’d interviewed many of the speakers and chairs for Development over the last few years, either in print or on screen, so have decided to share them with you here.
This year we are pleased to announce Professor Wolf Reik as our keynote speaker. His research group, based at the Babraham Institute, investigates the roles of epigenetic gene regulation in mammalian development.
We are also honoured to have Dr Susan Cox and Dr Germano Cecere as our outstanding invited speakers. Dr Susan Cox, from King’s College London, has a strong background in biophysics and has done quantitative analysis using super-resolution microscopy. Dr Germano Cecere, from the Institute Pasteur, focuses on the characterization of short-RNA-based mechanisms of epigenetic inheritanceduring animal development and upon environmental changes.
As it is traditional, we will end up the meeting with a panel discussion, this time dedicated to Publishing, Editing and Journals. There we will be able to hear the views and experiences of Jennifer McLennan, Head of External Relations at eLife, Robert Kiley, Head of Open Research at the Wellcome Trust, and Katherine Brown, Executive Editor of Development.
Finally, we are looking for additional talks and posters from PhD students and postdoctoral researches who work on the fields of Evo-Devo, Stem Cell Biology, Embryology or more general Developmental Biology. Experimental and theoretical approaches are equally acceptable.
Whether you want to submit an abstract for a talk or poster, or just attend the meeting, you can register here. Registration is free, and there will be prizes for the best talks and posters.
Deadline for abstract submission is midnight on 14th April 2018.
Last day tomorrow to apply for the EMBO practical course on 3D Developmental Imaging (April 11th!).
Are you a developmental biologist struggling with 3D imaging (confocal, 2p, light-shet, OPT)? Don’t miss this opportunity: registration fee INCLUDES meals, course materials, hotel and local transport, all made possible by generous sponsorship from EMBO, the Gulbenkian Institute and our commercial partners. EMBO provides in addition a limited number of travel grants for candidates from Croatia, Czech Republic, Estonia, Greece, Hungary, Italy, Malta, Lithuania, Poland, Portugal, Slovakia, Slovenia, Spain and Turkey and Chile, India, Singapore and Taiwan.
There is a vacancy for a postdoctoral research fellow position at the Sars International Centre for Marine Molecular Biology (www.sars.no) in the research group headed by Dr. Pawel Burkhardt. The position is for a period of 4 years and is funded on the Sars Centre core budget. The Sars Centre belongs to the University of Bergen and is partner of the European Molecular Biology Laboratory (EMBL) (www.embl.de). The place of work will be at the Sars Centre. The starting date is negotiable but preferably no later than 01 September 2018.
About the project/work tasks: The Burkhardt group combines comparative biological systems in the laboratory to understand when and how the first synapses and neurons evolved. The group is particularly interested in studying the origin and evolution of synaptic proteins (Burkhardt et al, 2011 PNAS; Burkhardt et al, 2014 MBE; Bhattacharyya et al, 2016 eLife). We are looking for a highly self-motivated and enthusiastic Postdoctoral Research Fellow with interests in evolutionary biology, neurobiology and cell biology. The project will focus on the characterization of synaptic protein homologs in sponges and ctenophores to better understand the evolution of first neuron-like cell types in animals. The successful candidate will undertake research with the possibility to use a variety of techniques, ranging from super resolution immunofluorescence and electron microscopy, biochemical methods (protein purification, co-IPs, and analytical ultracentrifugation), mass spectrometry to X-ray crystallography to study synaptic protein homologs in sponges and ctenophores. The successful candidate will work in close association with the group leader and other lab members with the aim to eventually contribute to the further development of the project in line with her/his interests.
Qualifications and personal qualities:
The applicant must hold a Norwegian PhD or an equivalent degree or must have submitted his/her doctoral thesis for assessment prior to the application deadline. It is a condition of employment that the PhD has been awarded
Strong motivation/enthusiasm to perform research at an internationally competitive level
Practical experience in biochemical techniques (protein purification, Co-IPs) and with different fluorescence imaging techniques is highly desirable
Specific experience with sponges or ctenophores is beneficial, but not essential
The ability to work both independently and to cooperate with others in a structured manner is essential
Proficiency in both written and oral English
About the position of postdoctoral research fellow:
The position of postdoctoral research fellow is a fixed-term appointment with the primary objective of qualifying the appointee for work in top academic positions. The fixed-term period for this position is 4 years. Individuals may not be hired for more than one fixed-term period as a postdoctoral research fellow at the same institution. Upon appointment, applicants must submit a project proposal for the qualifying work including a work schedule. It is a requirement that the project is completed in the course of the period of employment.
We can offer:
A professional, challenging and international working environment.
Well-equipped, modern laboratories and facilities
Salary at pay grade 57 (code 1352 / pay range 24, alternative 1) according to the state salary scale upon appointment. This constitutes a gross annual salary of NOK 490.900. Further promotions are made according to length of service. For particularly highly qualified applicants, a higher salary may be considered
Enrolment in the Norwegian Public Service Pension Fund (SPK)
A position in an inclusive workplace (IA enterprise)
Good welfare benefits
Your application in English must include:
A cover letter of the applicant’s research interests and motivation for applying for the position.
The names and contact information for at least two reference persons. One of these must be the the main advisor from the PhD programme.
CV including most relevant (i.e. first author) published papers and pre-prints
Transcripts and diplomas and official confirmation that the doctoral thesis has been submitted
Relevant certificates/references
List of any works of a scientific nature (publication list)
Detailed information about the position can be obtained by contacting: Group Leader Pawel Burkhardt, tlf.: +47 55 58 43 57, email: Pawel.Burkhardt@uib.no.
The state labour force shall reflect the diversity of Norwegian society to the greatest extent possible. Age and gender balance among employees is therefore a goal. People with immigrant backgrounds and people with disabilities are encouraged to apply for the position.
We encourage women to apply. If multiple applicants have approximately equivalent qualifications, the rules pertaining to moderate gender quotas shall apply.
The University of Bergen applies the principle of public access to information when recruiting staff for academic positions.
Information about applicants may be made public even if the applicant has asked not to be named on the list of persons who have applied. The applicant must be notified if the request to be omitted is not met.
Further information about our employment process can be found here.
There is a vacancy for a PhD position at the Sars International Centre for Marine Molecular Biology (www.sars.no) in the research group headed by Dr. Pawel Burkhardt. The position is for a fixed-term period of 4 years and is subject to funding on the Sars Centre core budget. The Sars Centre belongs to the University of Bergen and is partner of the European Molecular Biology Laboratory (EMBL) (www.embl.de). The place of work will be at the Sars Centre. The starting date is negotiable but preferably no later than 01 September 2018.
About the project/work tasks: The goal of the Burkhardt group is to reconstruct the evolutionary origin of synapses and neurons. The group is particularly interested in studying synaptic protein homologs in choanoflagellates, sponges and ctenophores. We are looking for a highly self-motivated and enthusiastic PhD student with interests in evolutionary biology, neurobiology and cell biology. The project will focus on when the protein signalling complexes required for synaptic activity first evolved and how they functioned at a molecular level (Burkhardt et al, 2011 PNAS; Burkhardt et al, 2014 MBE; Bhattacharyya et al, 2016 eLife). The successful candidate will undertake research with the possibility to use a variety of techniques, ranging from super resolution immunofluorescence and electron microscopy, various biochemical methods to X-ray crystallography to study synaptic protein homologs in choanoflagellates. The successful candidate will work in close association with the group leader and other lab members with the aim to eventually contribute to the further development of the project in line with her/his interests.
Qualifications and personal qualities:
The applicant must hold a master’s degree or the equivalent or must have submitted his/her master’s thesis for assessment prior to the application deadline. It is a condition of employment that the master’s degree has been awarded
Routine experience in standard molecular and cellular biology techniques is required
Practical experience in biochemical techniques (protein purification, Co-IPs) and with different fluorescence imaging techniques is highly desirable
Specific experience with choanoflagellates is beneficial, but not essential
The ability to work both independently and in a structured manner, cooperate with others and a possess high motivation and enthusiasm is essential
Proficiency in both written and oral English
About the PhD:
The duration of the PhD position is 4 years, of which 25 per cent of the time each year comprises required duties associated with research, teaching and dissemination of results. The employment period may be reduced if you have previously been employed in a recruitment position.
About the research training:
As a PhD Candidate, you must participate in an approved educational programme for a PhD degree within a period of 4 years. A final plan for the implementation of the research training must be approved by the faculty within three months after you have commenced in the position. It is a condition that you satisfy the enrolment requirements for the PhD programme at the University of Bergen.
We can offer:
A professional, challenging and international working environment
Well-equipped, modern laboratories and facilities
Salary at pay grade 50 (Code 1017/Pay range 20, alternative 8) in the state salary scale. Currently equal to NOK 436.900. Further promotions are made according to qualifications and length of service in the position
Enrolment in the Norwegian Public Service Pension Fund (SPK)
A position in an inclusive workplace (IA enterprise)
Good welfare benefits
Your application in English must include:
A brief account of the applicant’s research interests and motivation for applying for the position
The names and contact information for two reference persons. One of these must be the main advisor for the master’s thesis or equivalent thesis
CV
Transcripts and diplomas showing completion of the bachelor’s and master’s degrees, or official confirmation that the master’s thesis has been submitted
Relevant certificates/references
A list of any works of a scientific nature (publication list)
Detailed information about the position can be obtained by contacting: Group Leader Pawel Burkhardt, tlf.: +47 55 58 43 57, email: Pawel.Burkhardt@uib.no
The state labour force shall reflect the diversity of Norwegian society to the greatest extent possible. Age and gender balance among employees is therefore a goal. It is also a goal to recruit people with immigrant backgrounds. People with immigrant backgrounds and people with disabilities are encouraged to apply for the position.
We encourage women to apply. If multiple applicants have approximately equivalent qualifications, the rules pertaining to moderate gender quotas shall apply.
The University of Bergen applies the principle of public access to information when recruiting staff for academic positions.
Information about applicants may be made public even if the applicant has asked not to be named on the list of persons who have applied. The applicant must be notified if the request to be omitted is not met.
The successful applicant must comply with the guidelines that apply to the position at all times.
Cell fate commitment relies on both activation of appropriate genes and suppression of inappropriate ones. Polycomb group proteins are known to be crucial epigenetic silencers of developmental genes, but the manner by which they control fate in vivo, and the relative roles of different Polycomb proteins in silencing, have remained unclear. A new paper in Development tackles this problem using the Drosophila eye a developmental model – we caught up with authors Jinjin Zhu and Justin Kumar, Professor of Biology at Indiana University in Bloomington, to find out more.
Jinjin and Justin
Justin, can you give us your scientific biography and the questions your lab is trying to answer?
JK I started my career in Drosophila eye development while I was an undergraduate in the laboratory of Karl Fryxell at the University of California, Riverside. He was a wonderful mentor and it was my time in his lab that convinced me that I wanted to be a professor one day. While I was in Karl’s lab, I read Don Ready’s seminal paper on the morphogenetic furrow (Ready et al., 1976) and was totally amazed by the cellular mechanism of pattern formation. From the images in the paper, I could see a field of undifferentiated cells being transformed into the periodic units of photoreceptor clusters right before my eyes. I knew then that I wanted to join his lab for my PhD studies. Being in Don’s lab at Purdue University as a graduate student was a privilege. He taught me how to love the fly eye for its own sake and to appreciate its intrinsic beauty.
I then went on to do my post-doctoral fellowship with Kevin Moses initially at the University of Southern California and then at Emory University. It was in Kevin’s lab that I finally settled on the research questions that still drive me today. I stumbled on what I thought to be an astonishing phenotype. Quite by accident I discovered that manipulations of the Notch and EGF Receptor signalling pathways led to the homeotic transformation of the eye into an antenna. While Hox mutants change entire body segments, I was able to observe fate transformations occurring within a single imaginal disc. When I joined the faculty of Indiana University I set out to understand how the fly eye-antennal disc is first set apart from the other discs (i.e. leg, wing, haltere, genital) and then how it is later subdivided into distinct territories such as the compound eye, ocelli, antenna, maxillary palps, and head epidermis. Over the years my research group has discovered that while gene regulatory networks promote fate specification, growth, and patterning, they also influence development by repressing alternate and inappropriate tissue fates. My current interests are to understand how the retinal determination gene regulatory network cooperates with signalling pathways and epigenetic complexes to prevent the eye from adopting distant fates such as the wing and more local fates such as the head epidermis.
And Jinjin how did you come to be involved with this project?
JZ I was really interested in the fate transformation caused by mis-expression of Hox genes when I was in college. When I joined the Justin’s lab, I did a genetic screen to find upstream regulators of eyeless in the developing eye disc. I knocked down eyeless and Sfmbt together and found this amazing eye-to-wing transformation phenotype. Meanwhile, Ali Ordway (second author) joined the lab and decided to screen other PcG proteins. She knocked down Pc and saw similar phenotypes. We were both fascinated by the images of these chimera tissue, in which the dorsal part of the eye disc turned into a wing disc while the ventral part remained as an eye disc, so we decided to figure out what happened to these mutant discs.
A selection of eye and wing discs from Fig. 1 in the paper.
How did you come to be interested in the phenomenon of transdetermination?
JK I got interested in transdetermination purely by accident. When I joined Don’s lab in 1991, I made sure that I read every paper that he had published. In one of his papers, he and Ricky Lebovitz had transplanted eye-antennal disc fragments into host larvae and then recovered the tissue after the host had emerged as an adult (Lebovitz and Ready, 1986). These experiments were aimed at understanding if the morphogenetic furrow was pushed or pulled across the eye field. I was really intrigued by the disc transplantation method used in his paper so I started reading about the history of this method, which I learned was pioneered by Beadle and Ephrussi in the 1930s. In the course of these readings I came across the work of Ernst Hadorn. It was from his papers that I learned about the concepts of determination and transdetermination. When Jinjin and I saw the eye to wing transformation, it reminded me of the fact that Hadorn remarked that the eye could only transdetermine into a wing. And it was at that point that I realized that the loss of PcG and Pax6 that we noticed gave the eye to wing switch might be the molecular explanation for the eye to wing transdetermination event that Hadorn observed many decades ago.
Third instar larval eye-antennal disc following Pc RNAi, from Fig. 2 in the paper.
Can you give us the key results of the paper in a paragraph?
JK In this paper we demonstrate that the Pax6 transcription factor and the Polycomb group (PcG) of epigenetic silencers prevent the eye from adopting a wing fate. This decision is made early in development during the last stages of embryogenesis and during the first larval instar. The eye transforms into a wing because the chromatin around the Antp locus fails to be compacted thereby allowing for its activation by the zinc finger transcription factor Teashirt (Tsh), which is normally expressed in and required for the specification of the eye. Our findings suggest that in addition to promoting the primary fate of a tissue or organ, gene regulatory networks must play defense and suppress the activation of inappropriate selector genes and/or entire gene regulatory networks. This repressive activity appears to require cooperation from epigenetic silencing complexes such as PcG.
Ectopic wings in Pax6 / Sfmbt double knockdown flies, from Fig. 5 in the paper
Why do you think the dorsal region of the eye might be more susceptible to wing transformation than the ventral region?
JZ This is a very interesting question and I think the answer lies down to the gene regulatory network controlling dorsal eye disc. 1) Wingless (wg), which is normaly required for wing development, is expressed in a higher level in the dorsal eye disc than in its ventral compartment. 2) engrailed (en) and cubitus interruptus (ci), which regulates A/P compartment of the wing disc also meets in the dorsal portion of the eye disc. Thus, the expression pattern of the endogenous genes in the dorsal eye disc contributes a lot to the eye-to-wing fate transformation. In addition, the dorsal eye disc is more susceptible to adopt wing fate because the level of Pax6 is significantly lower in the dorsal eye disc, especially in the region which will become the future dorsal head capsule. We have demonstrated that eye disc is more resistant to loss of Sfmbt function than the antennal disc. This is very likely due to the presence of Pax6 in the eye progenitor cells, because simultaneously knocking down Pax6 and Sfmbt induces the fate transformation.
It must have been particularly satisfying to discover the molecular underpinnings of phenomena first described in the pre-molecular biology age?
JK Yes, it was indeed satisfying to provide a modern perspective to an old problem/observation. In general I really enjoy reading the literature from the pre-molecular age – that is how I got interested in transdetermination in the first place. I also like scour the older literature for problems in eye development that were once studied but later abandoned due to the lack of the right genetic or molecular tools. If you look carefully enough, there is a wealth of such studies out there that are ripe for a modern perspective. For example, one of the exciting new areas of research in my laboratory today is the role that the peripodial epithelium, a tissue that overlies the eye-antennal disc, plays in development. There were several papers in the 1970s that suggested that its role was limited to the fusion of the two eye-antennal discs during pupal development. However, between 2000-2002 several laboratories provided evidence that signalling existed between these two tissues. But very little has been done since on this topic. Now several researchers in my lab are looking at the role that transcriptional networks in the peripodial epithelium play in promoting the fates of the eye-antennal disc.
I also like how researchers of times past thought about development. The Epigenetic Landscape Model by C.H. Waddington is one of my favourite examples. To represent the process by which individual cells make fate decisions, he proposed that a cell can take different paths during development with each path representing a journey towards a unique fate. He drew a diagram to represent this idea – in his drawing a ball rolling down a mountainside presented a cell on its way to adopting a final fate. This drawing and the concepts that it represents is very inspiring to me. One can think about how to push cells developmentally down different trails or how to push the cells uphill (de-differentiation) and then down another trail (fate reassignment). For my own work, I try to think of the ball not as a single cell. Instead, to me it represents the entire eye-antennal disc. My lifetime goal is to figure out how the eye-antennal disc is guided down the mountain and how it ultimately gives rise to five distinct tissues and organs.
Sfmbt loss-of-function clones in eye-antennal discs, from Fig. 5 in the paper
When doing the research, did you have any particular result or eureka moment that has stuck with you?
JZ Yes. For a long time, I couldn’t figure out why the eye disc adopts a wing fate but not any other tissue fates. I know it is likely due to the de-repression of Antp in the developing eye when PcG activity is impaired. However, why is Antp being activated when the epigenetic silencers are removed? This question was solved when a piece of data came back from another ongoing project, in which I found that over-expression of teashirt (tsh) was able to rescue the headless phenotype of Pax6 double mutant (Zhu et al, 2017). In those flies, little wings or thoracic bristles were found in the rescued head cuticle, so I wonder the endogenous expression of tsh might be the transcriptional activator of Antp when Pc is removed from the eye disc. I did an experiment to knockdown Pc and Tsh (Figure 3) at the same time and it turn out to be true. Tsh is required to activate Antp during the fate transformation. Although we do not know whether Tsh directly turns on Antp transcription or not, but at least we found some underlying mechanisms of the homology between the eye and the wing. I think the lesson here is to have multiple projects going on at the same time.
And what about the flipside: any moments of frustration or despair?
JZ For me, the frustration in this project is that isolating eye discs at early stages, such as in 1st and early 2nd larval instar, is almost impossible. Thus, we couldn’t verify our final model of PcG proteins being recruited to the genome at these specific stages using ChIP-Seq. I hope the techniques will advance and allow us to reveal how exactly these epigenetic regulators function in vivo.
What next for you Jinjin – I hear you’ve moved to Harvard?
JZ Yes, for my postdoctoral training, I will work with Dr. Robert Kingston, focusing on how PcG proteins control gene expression in mammalian system. The PcG proteins in mammals are much more complicated than in Drosophila. Different PcG complexes have multiple variants and each protein have multiple homologs. Thus, a diversity of possible mechanisms that might be used to generated a repressive state of gene expression, such as histone modification, chromatin compaction and higher-order genome organization. I think the eye-to-wing transformation project has brought me here, but I want to learn more about the underlying mechanisms of epigenetic regulators on the molecular level for my future research.
Where will this work take the Kumar lab?
JK My research group has started studying how the interplay between transcriptional networks and epigenetic complexes such as Polycomb, Trithorax, and SAGA controls fate specification within the eye-antennal. These studies build upon the findings of our paper described here in Development in which Pax6 and PcG proteins cooperate to repress wing fates from being adopted in the developing eye. Currently, we have evidence that Pax6 cooperates with Trithorax and SAGA complexes to control the number of antennae that are produced. We also have evidence that these same complexes work together to prevent the duplication of the entire eye-antennal disc. I am very excited about these preliminary findings and I think my lab, for the near future, will be focused on using the tissues within the eye-antennal disc to revisit several very basic questions – how does an organism control the fate, number, and placement of all of the organs that it needs for survival.
Finally, let’s move outside the lab – what do you like to do in your spare time?
JZ I travel with my husband during holidays and we have been to many national parks in US. We both like photographing wild animals. At home, I usually play piano and computer games if I don’t need to collect fly embryos.
JK When I am not in the lab or my office I enjoy playing tennis. It is a terrific sport and a good outlet to release stress. I try to mix tennis and work as well whenever possible. When I am at home working on a paper or grant, I have the Tennis Channel on in the background. If there is an important match, I will stream it on my work computer as well. I also take my camera wherever I go and enjoy photographing wild life and outdoor scenery.
We have an opening for a postdoctoral position that will address fundamental questions in small RNA biology, genomic conflict, and speciation.
What is endogenous RNAi utilized for? We earlier described a mysterious class of endo-RNAi substrates termed hpRNAs (Okamura Nature 2008), and recently recognized that these mediate adaptive gene regulation in testis (Wen Molecular Cell 2015). These data open a window on a vital biology of RNAi, and now lead us to explore the evolution and function of RNAi systems across the Drosophilid phylogeny.
We discovered networks of rapidly evolving RNAi substrates we hypothesize resolve intragenomic conflicts, and successfully started to use CRISPR/Cas9 in non-model fly species to test some of these ideas (Lin 2018, in submission). Amazingly, while endogenous RNAi was not historically thought to have much phenotypic impact, we find that rapidly evolving genomic battles are being waged and critically depend upon the powerful weapon of RNAi silencing to propagate the species. Reciprocally, we are fascinated to understand by what novel molecular mechanisms de novo selfish meiotic factors can paradoxically drive population extinction.
We seek a motivated postdoctoral fellow with strong Drosophila molecular genetics experience and interest in integrating genome engineering, biochemistry, and bioinformatics to analyze the evolution and function of RNAi silencing systems in resolving deleterious intragenomic conflicts in testis. Although our entry point is RNAi biology, we anticipate that selfish factors yet to be discovered may mediate their effects through chromatin mechanisms.The successful candidate will integrate into a team that is actively engaged in diverse topics in gene regulation in Drosophila and mammalian models, and the Sloan-Kettering Institute provides a vibrant research community.
Funded position with housing and medical benefits are available immediately. Please provide CV, motivation letter and references to Eric Lai, laie@mskcc.org.
Relevant recent papers on hpRNAs and testis post-transcriptional regulation.
see also https://www.mskcc.org/research-areas/labs/eric-lai
Lin, C.-J., F. Hu, R. Dubruille, J. Wen, J. Vedanayagam, P. Smibert, B. Loppin and E. C. Lai (2018). The hpRNA/RNAi pathway is essential to resolve intragenomic conflict to preserve balanced sex ratio. Submitted.
Mohammed, J., A. Flynt, A. Panzarino, M. Mondal, M. DeCruz, A. Siepel and E. C. Lai (2018). Deep experimental profiling of miRNA diversity, deployment, and evolution across the Drosophila genus. Genome Research28: 52-65.
Kondo S., J. Vedanayagam, J. Mohammed, S. Eizadshenass, L. Kan, N. Pang, R. Aradhya, A. Siepel, J. Steinhauer and E. C. Lai (2017). New genes often acquire male-specific functions but rarely become essential in Drosophila. Genes and Development31: 1841–1846. (Highlighted in Genes and Dev 31: 1825-1826.)
Lin, C.-J., J. Wen, F. Bejarano, F. Hu, D. Bortolamiol-Becet, L. Kan, P. Sanfilippo, S. Kondo and E. C. Lai (2017). Characterization of a TUTase/RNase complex required for Drosophila gametogenesis. RNA23: 284-296.
Wen, J., H. Duan, F. Bejarano, K. Okamura, L. Fabian, J. A. Brill, D. Bortolamiol-Becet, R. Martin, J. G. Ruby and E. C. Lai (2015). Adaptive regulation of testis gene expression and control of male fertility by the Drosophila hairpin RNA pathway. Molecular Cell57: 165-78.
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Born in 1943, 
Thereafter he held positions as Edward Penley Abraham Research Professor of the Royal Society (2003-8), honorary Visiting Professor at the University of York (2007-16), and is now an Associate at the University of Oxford and Emeritus Student of Christ Church, Oxford.
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