2023 article
Obituary Philip N. Benfey (1953-2023)
Bennett, M. J., Brady, S. M., Dinneny, J. R., Helariutta, Y., & Sozzani, R. (2023, November 20). DEVELOPMENTAL CELL, Vol. 58, pp. 2413–2415.
www.cell.com (publisher PDF)
Source: Web Of Science
Added: January 2, 2024
“When I started to work in systems biology, I kept running across this term ‘emergent behavior,’ and it was really not clear to me, and so as with many things for me, an analogy was very helpful. The analogy I’d like to propose to you is that of a flock of birds, the idea being the following, that you can study a single bird as much as you like and you will never understand how a flock works, because a flock is all about the interactions between birds, and those interactions can lead to some really interesting complex behavior …”—Philip Benfey Professor Philip Benfey, a leading figure in plant biology, passed away on September 26, 2023, at the age of 70. Philip will be deeply missed by his family and friends. He adored his wife, Elisabeth, and their children, Sam and Julian. He was very proud of their achievements. We extend our heartfelt condolences to them as well as to his wider family, his current and former trainees, and his colleagues and friends as we all mourn his loss. Philip has been a giant presence in the field of plant biology over the past several decades—literally, scientifically, and legacy-wise. Everyone who met Philip could not help but be impressed by his imposing physical presence, his intelligence, and his scientific vision. Philip considered himself an “accidental scientist,” who after touring the world for 6 years ended up at the University of Paris VI. From there he went to graduate school at Harvard Medical School, where he completed his thesis with Phil Leder. Thereafter, he performed postdoctoral work with Nam-Hai Chua at the Rockefeller University. His independent career featured several distinct phases and approaches, each marked by a seminal scientific discovery or research innovation. Philip’s impressive independent career took off at NYU, where he adopted the Arabidopsis root as his experimental model to study the genetic regulation of plant development. He pioneered genetic screens to isolate root mutants influencing radial patterning. As a result, his lab identified a pair of GRAS family transcription factors, SHORT-ROOT (SHR) and SCARECROW (SCR), that specify the asymmetric cell division and subsequent cell specification processes separating endodermal and cortex tissue identities. Philip’s team later discovered that SHR is a mobile transcription factor that is produced in the innermost vascular domain of the root and moves from there, through the plasmodesmata, to the adjacent endodermal/cortex stem cell.1Nakajima K. Sena G. Nawy T. Benfey P.N. Intercellular movement of the putative transcription factor SHR in root patterning.Nature. 2001; 413: 307-311https://doi.org/10.1038/35095061Crossref PubMed Scopus (648) Google Scholar In this stem cell, SHR then forms a complex with SCR, and this complex is required for the asymmetric division separating the two cell layers. The formation of this complex also provides a sequestration mechanism to restrict the further movement of SHR and thereby to regulate the number of cell layers in the root. Although prior to this study it had been shown that proteins, even transcription factors, can move through plasmodesmata, the SHR-SCR model on radial patterning was the first to highlight the importance of mobile transcription factors, today a widely recognized principle of plant development. Throughout this period, Philip’s team worked closely with the lab of Ben Scheres at Utrecht University, investigating the interaction of the SHR-SCR module with other transcription factors and developmental signals that define radial patterning and provide the basis for our current understanding. After moving to Duke in 2002, Philip published a series of highly influential papers describing a transformative research approach. While plant single-cell transcriptomics are now de rigueur, his work was truly ahead of its time. Philip believed that resolving gene expression in Arabidopsis root tissues in space and time could help identify the full complement of factors required for cell-type patterning and acquisition of identity. He, along with Ken Birnbaum, took advantage of fluorescent activated cell sorting (FACS) coupled with the many transcriptional reporter lines that mark individual cell types or populations of cell types in the root. FACS was and is a frequently used tool in animal research, but he was able to convince cytometry facility operators to let plant biologists load in their protoplasts to have the machine recognize GFP-positive cells; and scientists in the lab trained in RNA extraction from very small sample sizes. Microarray analysis on this material subsequently reported near-transcriptome-scale gene expression. Since a cell’s developmental trajectory can be tracked along the root’s longitudinal axis, simply cutting a root into several pieces along this axis and isolating RNA/performing microarray analysis, plus some clever computational tools, could capture gene expression in time over the root’s longitudinal axis. Successive papers in Science, including Brady et al., 2007,2Brady S.M. Orlando D.A. Lee J.Y. Wang J.Y. Koch J. Dinneny J.R. Mace D. Ohler U. Benfey P.N. A high-resolution root spatiotemporal map reveals dominant expression patterns.Science. 2007; 318: 801-806https://doi.org/10.1126/science.1146265Crossref PubMed Scopus (888) Google Scholar demonstrated a wealth of expression pattern types and their changes over a cell type’s developmental trajectory. These data are now used by scientists all over the world to determine the expression pattern of their gene(s) of interest. These methods were used to further profile whole-transcriptome gene expression when RNAseq was in its infancy, followed by small RNA levels, protein, and metabolite abundance. These datasets served as a framework for the annotation of every single-cell transcriptome paper that has recently been published. Philip next pioneered systems biology approaches to propel the field of plant developmental biology forward to become more predictive and quantitative. His team exploited these approaches to discover how asymmetric cell division is regulated in roots. By cleverly utilizing fluorescence-activated cell sorting and single-cell gene expression analysis, he discovered a direct connection between developmental subnetworks and the cell division machinery. Philip later explored how emergent behavior transcends a series of switches influenced by high (for asymmetric cell divisions) and low concentrations (for symmetric cell divisions) of proteins. Philip recognized that to understand complex regulatory processes it is critical to quantitatively analyze protein movement and protein-protein interactions in time and space. This led Philip and Ross Sozzani’s teams to study the SHR-SCR regulatory network, where intercellular movement of SHR and interaction with its target SCR controls root patterning and cell fate specification.3Clark N.M. Hinde E. Winter C.M. Fisher A.P. Crosti G. Blilou I. Gratton E. Benfey P.N. Sozzani R. Tracking transcription factor mobility and interaction in Arabidopsis roots with fluorescence correlation spectroscopy.Elife. 2016; 5e14770Crossref Scopus (68) Google Scholar Key parameters such as SHR mobility, oligomeric state, and association with SCR were quantified using advanced spectroscopy techniques and incorporated into a mathematical model. This seminal quantitative systems biology paper revealed that the timing of SHR protein movement and SHR-SCR stoichiometry play critical regulatory roles during root development. While able to generate seminal research discoveries at the disciplinary interface, Philip considered himself first and foremost a developmental biologist and used plants as an ideal model system to explore questions of cell fate determination. However, the standard practice in developmental biology, of minimizing the impact of the environment on the organism to study such processes, is counter to the nature of roots, which grow in intimate association with the complex and dynamic soil environment. If tissue-specific transcriptomics revealed a rich regulatory landscape for each cell, how much of this architecture was dependent on the specific environmental conditions under which the plants were grown? To address this question, Philip’s lab generated the first spatial maps of roots exposed to environmental stresses, including iron and sulfur deprivation, high salinity, and low pH.4Dinneny J.R. Long T.A. Wang J.Y. Jung J.W. Mace D. Pointer S. Barron C. Brady S.M. Schiefelbein J. Benfey P.N. Cell identity mediates the response of Arabidopsis roots to abiotic stress.Science. 2008; 320: 942-945https://doi.org/10.1126/science.1153795Crossref PubMed Scopus (599) Google Scholar Many of the transcriptional responses were regulated in a cell-type-specific manner, which resulted in major shifts in cell-type function, with many canonical functions only occurring under a narrow range of environmental conditions. Thus, this work showed that plants offered profound insights into the intricacies of cell identity. This identity is intrinsically linked to the environment, which serves as a critical factor in determining how this cellular property is realized through gene expression. While Philip was a stalwart proponent of Arabidopsis as a model system, his interest in understanding plants with more complex root systems, and in applying this knowledge to solve real-world problems, led to deep dives into the use of crop plants, especially rice, and the development of innovative phenotyping approaches. From custom-fabricated microfluidic devices to the use of optical tomography and image analysis algorithms, which generated three-dimensional representations of root system architecture,5Topp C.N. Iyer-Pascuzzi A.S. Anderson J.T. Lee C.-R. Zurek P.R. Symonova O. Zheng Y. Bucksch A. Mileyko Y. Galkovskyi T. et al.3D phenotyping and quantitative trait locus mapping identify core regions of the rice genome controlling root architecture.Proc. Natl. Acad. Sci. USA. 2013; 110: 1695-1704Crossref PubMed Scopus (0) Google Scholar Philip was essential in identifying nascent technologies that could be applied to this emerging area. Such work inspired Philip to establish two companies, Grassroots Biotechnology and Hi Fidelity Genetics, which leveraged these innovative methods to advance crop biotechnology solutions. Philip’s impact on the field of plant biology extends far beyond his pioneering basic and applied research discoveries and the technological innovations outlined above. What set Philip apart from his peer group was the unparalleled roll call of international researchers who worked in his laboratory and are now leaders in the plant biology field around the world. These several generations of researchers Philip has mentored arguably represent his greatest scientific legacy.