Transcending boundaries: from quantitative genetics to single genes

It is with great pleasure that we introduce this special issue of the Journal of Neurogenetics honouring Professor Marla Sokolowski’s career and outstanding scientific achievements. Marla’s foundational discoveries in fruit flies, honey bees, ants, rodents and humans have shaped fundamental concepts in behavioural genetics and evolutionary biology. Marla’s research has demonstrated the importance of individual differences in behaviour (reviewed in Anreiter & Sokolowski, 2019), that behaviour arises from complex interactions between genes and the environment, or gene-environment interplay (reviewed in Anreiter, Sokolowski, & Sokolowski, 2018) and addressed the mechanisms of biological embedding (reviewed in Aristizabal et al., 2020). Over the years Marla’s work has transcended the boundaries of conventional fields and has crossed over into many diverse research areas. Her ability to develop this distinctive research approach was evident from early on. Marla completed her undergraduate degree in Zoology at the University of Toronto in 1977. Her graduate training was unique, as she did not seek out a mentor or lab that specialized in a particular research area. Instead, she looked for a mentor that would let her follow up on observations she made as an undergraduate student regarding differences in Drosophila larval behaviour. After having been discouraged to pursue this area of research by other professors, Marla convinced Professor Roger Hansell to allow her to pursue the genetics of this behavioural difference in his mathematical ecology lab. Four years later, Marla’s original ideas not only allowed her to complete a PhD in Behaviour Genetics at the University of Toronto (in 1981), but her findings also became the basis for her internationally recognized forty-year long research program. Following her PhD, Marla would pursue postdoctoral research at York University, where she received an NSERC University Research Fellowship position, which was designed to keep promising young researchers in Canada. In 1986 Marla was offered a faculty position at York University. She would later move her lab to the Mississauga campus of the University of Toronto in 1999, where she was named a University Professor in 2010, and then move again to the downtown campus of the University of Toronto in 2012. While leading a thriving research group, Marla also actively led outreach activities fostering scientific collaboration across disciplines. At the University of Toronto Mississauga, she served as the Co-director of the Genes, Environment, Nervous System and Behaviour Research Cluster. Later, at St. George, she became the Academic Director of the Fraser Mustard Institute for Human Development, and Co-Director of the Child and Brain Development Program, funded by the Canadian Institute for Advanced Research (CIFAR). Over the course of her career, Marla has received numerous awards and accolades, such as a Canada Research Chair in Genetics and Behavioural Neurology, numerous Distinguished Visiting Professorships and Awards of Excellence, University Professor of the University of Toronto, Queen Elizabeth II Diamond Jubilee Medal, Weston Fellow of the Canadian Institute for Advanced Research, and in 2020, she became only the second woman to win the Flavelle Medal of the Royal Society of Canada.

Transcending boundaries and breaking the confinement of traditional scientific disciplines would become a consistent theme in Marla’s career, both in her research and her supervisory style. Marla has trained 23 postdoctoral fellows, 21 PhD students and 15 MSc students. One of her distinguishing features as a mentor was giving her trainees the same freedom to develop their own research path that she had as a PhD student. Over the years this led to her lab branching off into many new and exciting research areas and fields. Marla and her trainees have made significant contributions to diverse fields such as behaviour genetics, evolution and ecology, molecular genetics, physiology, epigenetics, and neuroscience. Marla has been fundamental in launching the successful research careers of many of her trainees, a number of which developed their own research programs on the basis of the research path that Marla encouraged them to follow during their time in her lab.

Marla is most well known for her discovery of two allelic variants, rovers and sitters, that differ in larval foraging behaviour (Sokolowski, 1980). To understand how and why these variants existed, she developed a new subdiscipline of behavioural genetics, one that explores the mechanistic and evolutionary significance of behavioural variation. She and her trainees would show that a gene that encodes a cGMP-dependent kinase was primarily responsible for differences in larval foraging behaviour between rovers and sitters (de Belle, Hilliker, & Sokolowski, 1989; Osborne et al., 1997). Marla and her group would name this gene foraging and go on to discover that it affects a number of behaviours and physiological processes (reviewed in Anreiter & Sokolowski, 2019), including adult foraging behaviour (Pereira & Sokolowski, 1993; Anreiter, Kramer, & Sokolowski, 2017), learning and memory (Kaun, Hendel, Gerber, & Sokolowski, 2007, Mery, Belay, So, Sokolowski, & Kawecki, 2007), sleep (Donlea et al., 2012), nociception (Dason et al., 2020), stress responses (Dawson-Scully, Armstrong, Kent, Robertson, & Sokolowski, 2007; Dawson-Scully et al., 2010) and neurotransmission (Renger, Yao, Sokolowski, & Wu, 1999; Dason, Allen, Vasquez, & Sokolowski, 2019). foraging‘s role in behaviour is conserved in organisms ranging from flies, honey bees and ants to humans (Ben-Shahar, Robichon, Sokolowski, & Robinson, 2002; Lucas & Sokolowski, 2009; Struk et al., 2019). In recent years, Marla and her trainees have studied the gene structure of foraging in detail and linked many of these phenotypes to specific promoters (Allen, Anreiter, Neville, & Sokolowski, 2017; Anreiter et al., 2017; Allen, Anreiter, Vesterberg, Douglas, & Sokolowski, 2018; Dason et al., 2020).

The special issue contains a combination of perspective, review and original research articles by four former Sokolowski lab postdocs (Jeffrey Dason, Ken Dawson-Scully, John Ewer and Christophe Lucas), nine current and former Sokolowski lab PhD students (Aaron Allen, Ina Anreiter, Yehuda Ben-Shahar, Steven de Belle, Mark Fitzpatrick, Karla Kaun, Sofia Pereira, Oscar Vasquez and Karen Williams), and twelve close colleagues and collaborators (Harold Atwood, Tom Boyce, Bertram Gerber, Stephen Goodwin, Ralph Greenspan, Jamie Kramer, Charalambos Kyriacou, Joel Levine, Catherine Rankin, Gene Robinson, Mariana Wolfner and Chun-Fang Wu).

We begin this special issue with three perspective articles by Marla’s husband, Allen Sokolowski (Sokolowski, 2021a), and their two children, Moriah Sokolowski (Sokolowski, 2021b) and Dustin Sokolowski (Sokolowski, 2021c). These three articles provide a fascinating look at Marla and her career from the perspective of her family. Next, Harold Atwood provides a perspective article on Marla’s academic journey, reviewing significant stages of her scientific career (Atwood, 2021). Ralph Greenspan then gives a personal account of Marla and describes how she successfully combined a classical behavioral-quantitative-genetic approach (Hirschian approach, named after Jerry Hirsch) with the other major Drosophila approach of studying single-gene mutations (Benzerian analysis, named after Seymour Benzer) (Greenspan, 2021). Next, three of Marla’s former PhD students, Sofia Pereira, Karen Williams, and Steven de Belle describe their time in the Sokolowski lab and Marla as mentor (Pereira, Williams, & de Belle, 2021), and finally Tom Boyce talks about his experiences with Marla at CIFAR (Boyce 2021).

The next set of articles consists of 4 review papers. Aaron Reiss and Catherine Rankin provide a review of Marla’s contributions to the field of behavioural genetics (Reiss & Rankin, 2021). Mariana Wolfner and colleagues provide a review on the role of octopamine in insect reproductive physiology and mating behavior (White, Chen, & Wolfner, 2021). Jamie Kramer and colleagues review courtship conditioning in Drosophila (Raun, Jones, & Kramer, 2021) and lastly, Christophe Lucas & Yehuda Ben-Shahar review the role of the foraging gene as a modulator of division of labour in social insects (Lucas & Ben-Shahar, 2021).

The next 7 papers are original research reports on the Drosophila foraging gene, the major focus of Marla’s career. Ina Anreiter and colleagues describe a vital role for foraging at the start of metamorphosis for subsequent adult emergence (Anreiter et al., 2021). Aaron Allen reports that foraging is primarily expressed in glia in the adult nervous system (Allen & Sokolowski, 2021). Jeffrey Dason demonstrates that glial foraging regulates synaptic function through effects on nerve terminal growth at the larval neuromuscular junction, whereas presynaptic foraging directly regulates neurotransmitter release (Dason & Sokolowski, 2021). Ken Dawson-Scully and Jennifer Krill characterize a novel stimulus-induced glial calcium wave in Drosophila larval peripheral segmental nerves and show that this response is modulated by foraging (Krill & Dawson-Scully, 2021). Karla Kaun and colleagues demonstrate that the foraging gene affects alcohol sensitivity, metabolism, and memory in Drosophila adults (Oepen, Catalano, Azanchi, & Kaun, 2021). Joel Levine and colleagues report a role for the foraging gene in social networks (Alwash, Allen, Sokolowski, & Levine, 2021). Mark Fitzpatrick and colleagues show a role for the foraging gene in oviposition decisions (Vesterberg, Rizkalla, & Fitzpatrick, 2021).

Finally, the issue includes six additional original research reports, one by Yehuda Ben-Shahar and Ross McKinney on Drosophila larval aggregation behavior (McKinney et al., 2021). Stephen Goodwin, Megan Neville, and colleagues generate and characterize a new fruitless core P1 promoter mutant (Neville et al., 2021). Chun-Fang Wu and Atulya Iyengar describe a fly seizure EEG that measures field potential activity in the Drosophila brain (Iyengar & Wu, 2021). Oliver Kobler, Bertram Gerber, and colleagues report a new protocol for the 3 D visualization of transgene expression across the whole body of Drosophila larva (Kobler et al., 2021). Gene Robinson and colleagues examine neurodevelopmental and transcriptomic effects of CRISPR/Cas9-induced somatic orco mutation in honey bees (Chen et al., 2021). Charalambos Kyriacou and Rosamund Stanley examine latitudinal cline in a Drosophila courtship song, finding that song interpulse interval is strongly associated with latitude (Stanley & Kyriacou, 2021).

Lastly, we provide a photo gallery of the many different eras of the Sokolowski lab (Anreiter & Dason, 2021). Marla has made a lasting impact on many fields with her discoveries. Marla’s willingness to cross boundaries into other fields has led to many fruitful collaborations and resulted in her trainees being spread out in many diverse fields. Her research mentorship style has led to her scientific progeny developing research programs in fields such as behaviour genetics, epigenetics, neuroscience, evolution and ecology, and molecular biology. In this special issue, we focus primarily on behaviour genetics and neuroscience. However, Marla has made many important discoveries in the field of evolution and ecology (Sokolowski, Pereira, & Hughes, 1997; Rodd, Reznick, & Sokolowski, 1997; Fitzpatrick, Feder, Rowe, & Sokolowski, 2007), which is largely not covered in this special issue and is deserving of a second tribute in a specialized journal of that field.

With this special issue, we honour Marla’s incredible career and thank her for her mentorship, guidance, and friendship.

Acknowledgements

The authors thank all the authors that contributed their articles to this special issue, including many of Marla’s former trainees, colleagues, friends, and family.

Disclosure statement

No potential conflict of interest was reported by the author(s).