Leaders in Cell Adhesion: An Interview with Richard Hynes,Pioneer of Cell–Matrix Interactions

Abstract

On a recent visit Richard O Hynes, FRS, HHMI, Daniel K. Ludwig Professor for Cancer Research at the Koch Institute for Integrative Cancer Research, MIT, graciously agreed to be interviewed in person for the first in Cell Communication and Adhesion's series on “Leaders in Cell Adhesion”. In this interview we discussed three things: 1) the early role of family, mentors, and luck on his career path; 2) his major discoveries of fibronectin, integrins and the evolution of extracellular matrix proteins; and 3) his role in, and thoughts on, current science policy. This interview reveals his characteristic calmness and infectious optimism, his spontaneous and down to earth sense of humor, and his great ability to place scientific questions in perspective. The interview, carried out on April 30^th 2013 is reported here verbatim with only minor editing for clarity.     

Interview with the retinoblastoma family members: Do they help each other?

The ultimate destiny of a cell to undergo division, differentiation, survival, and death results from an intricate balance between multiple regulators including oncogenes, tumor suppressor genes, and cell cycle associated proteins. Deregulation of the cell cycle machinery switches the phenotype from a normal cell to a cancerous cell. Fundamental alterations of tumor suppressor genes may result in an unregulated cell cycle with the accumulation of mutations and eventual neoplastic transformation. As such, one may define cancer as a genetic disease of the cell cycle. In this review, we will emphasize our current understanding of how the cell cycle machinery maintains cellular homeostasis by studying the consequences of its deregulation.     

Gero Miesenböck: instructing the nervous system. Interview by William A Wells

Gero Miesenböck uses light and genetically encoded sensors and actuators to observe and control neural activity. Having caused headless flies to fly at will, he is set to understand how the nervous system encodes behavior.New techniques often drive advances in cell biology. Gero Miesenböck has developed powerful tools that open up whole new regions of neurobiology.First came tools to measure neuronal activity. The synaptolucins (1), developed with Jim Rothman (Memorial Sloan-Kettering Cancer Center, New York, NY), were based on a luciferase fusion protein targeted to synaptic vesicles. Neuronal activity led to exocytosis, thus exposing the synaptolucin to an extracellular pool of its substrate luciferin. Later came a pH-sensitive GFP (pHluorin) that lit up when exocytosis propelled it from the acidic inside of the secretory vesicle to the neutral extracellular environment (2).Miesenböck started his own lab in 1999 and is currently at Yale University (New Haven, CT). His chARGe system turned light into neural activity: it co-opted a fly visual transduction pathway to detect light and convert it into a depolarizing signal in neurons (3). In a simpler phototrigger system, light removed the chemical protection from ligands, allowing them to bind and activate receptors that could be expressed in any neuron subset of interest (4). He used this latter system to get the headless flies flying. In contrast to direct electrical stimulation of neurons using electrodes, the phototrigger can control neuron subtypes that are dispersed amongst other cells, all the while leaving animals free to roam and behave.Open in a separate windowFigure 1A light-activated circuit gets a sluggish fly (left) moving (right).MIESENBÖCK/ELSEVIERMiesenböck has recorded the first images of information flow between specific classes of neurons in an intact brain (5), and he recently discovered a new kind of circuit within the olfactory system (6). This circuit spreads excitation laterally, perhaps helping to boost otherwise sub-threshold signals so they can be detected (6). We spoke to Miesenböck as he was preparing to move to the University of Oxford, UK, where he will be helping to build up neuroscience in the Department of Physiology.     

Are chronic diseases related to height? Results from the Portuguese National Health Interview Survey

This paper analyze the association between height and chronic diseases in Portugal and the extent to which this relationship is mediated by education. The sample upon which the analysis is based comprised those participants in the 2005/2006 Portuguese National Health Interview Survey (n = 28,433) aged 25–79. Logistic regressions measured the association of height with ten chronic diseases, adjusting for age, lifestyle, education, and other socioeconomic factors. Among women, an additional centimeter in stature significantly decreased the prevalence of asthma, chronic pain, and acute cardiac disease, by 0.057, 0.221, and 0.033 percentage points, respectively. Also, mental disorders were significantly less prevalent in the last quartile of height. Among men, an additional centimeter in height was associated with a 0.074 lower prevalence of asthma, and men in the last quartile of height were significantly less at risk of acute cardiovascular disease. There was no significant association between height and the risk of diabetes, high blood pressure, cancer, and pulmonary diseases. As for the impact of education, women with a tertiary level were on average 5.3 cm taller than those with no schooling; among men, the difference was almost 9 cm. Adjusting for education reduced the height-related excess risk of ill health by 36% on average among men, and by 7% among women. The analysis indicates that there is a significant association of height with several chronic conditions, and that education plays a mediating role in the height–health connection. By emphasizing the role of height and education as determinants of chronic conditions, this paper also highlights the role of conditions related to childhood health and socioeconomic background.     

Out of words: The æsthesodic cine‐eye of Robert Gardner: An Exegesis and Interview

Anthropological evaluations of the film work of Robert Gardner have been compromised by their reluctance to engage with it as art, and more broadly, to celebrate rather than vilify the aesthetic possibilities of the genre of ethnographic film. Even recent experiments with reflexivity have done little to challenge the realism that undergirds anthropological reception of non‐fiction film. By contrast, this article and interview considers Gardner's work as both anthropology and art. In particular, it addresses the evolving dialectic of the verbal and the visual in his films, from Bhinden Harbour (1951) to Passenger (1998). It also argues that recent efforts by anthropologists to rethink the concept of culture from a post‐semiotic perspective, foregrounding corporeal embodiment in the constitution of culture as much as the self, expand the theoretical boundaries of visual anthropology. In turn, it suggests that this reorientation towards sensation and perception should allow for a more approbatory understanding of Gardner's films.