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Hybridization in Ants
Interspecific hybridization is a relatively common occurrence within all animal groups. Two main factors make hybridization act differently in ants than in other species: eusociality and haplodiploidy. These factors serve to reduce the costs of interspecific hybridization in ants while simultaneously allowing them to take advantage of certain benefits. Eusociality may mitigate the effects of hybridization by allowing hybrids to be shunted into the worker caste, potentially reducing the effects of hybrid sterility. In haplodiploid species, males do not have a father. They instead develop from unfertilized eggs as haploid clones of their mother. This means that interspecifically mated queens do not completely sacrifice reproductive potential even if all hybrids are sterile because they can still produce fertile males. These factors in turn suggest that hybridization should be more common among the social Hymenoptera than other animal groups. Nevertheless, current data suggest that ants hybridize at rates similar to other animal groups, although these data are limited. Furthermore, there is a large amount of overlap between cases of interspecific hybridization and cases of genetic caste determination. A majority of the cases in ants where caste is determined primarily by genotype are associated with hybridization. However, it is not clear how these two phenomena are related, and more research is needed to answer this question. As a first step in answering these questions, I designed a set of microsatellite markers for use in African driver ants in the genus Dorylus. Additionally, to facilitate population genetics research in all ant species I aimed to develop a set of primers that are broadly applicable to most ant species, since PCR primers for microsatellite loci are often not useful outside the species for which they were designed. I identified 45 conserved microsatellite loci based on the eight ant genomes that were available at the time and designed primers for PCR amplification. Among these loci, I chose 24 for in-depth study in six species covering six different ant subfamilies. On average, 11.16 of these 24 loci were polymorphic and in Hardy-Weinberg equilibrium in any given species. The average number of alleles for these polymorphic loci within single populations of the different species was 4.59. This set of genetic markers will thus be useful for population genetic and colony pedigree studies across a wide range of ant species, supplementing the markers available for previously studied species and greatly facilitating the study of the many ant species lacking genetic markers. This work shows that it is possible to develop microsatellite loci that are both conserved over a broad range of taxa, yet polymorphic within species, and should encourage researchers to develop similar tools for other large taxonomic groups. After the development of these microsatellites, I used them to investigate a system of hybridization between two species of African driver ants. All driver ants belong to the subgenus (Anomma) in the genus Dorylus. They are swarm-raiding army ants with colonies that can have as many as 12 million individual ants. Colonies frequently migrate to new nest sites and conduct daily swarm-raids, capturing and eating any invertebrates or even small vertebrates in their path. Colonies are monogynous, and the queens are highly multiply mated, mating with as many as 20 males. A previous study suggested that hybridization occurs between Dorylus molestus and Dorylus wilverthi at a site in western Kenya. However, the extent and exact pattern of hybridization have remained unclear, and its possible effect on caste determination has not been investigated. I aimed to determine the extent and direction of hybridization by measuring how frequently hybrids occur in colonies of both species, and to investigate the possibility of genetic caste determination. I show that hybridization is bidirectional and occurs at equal rates in both species. Hybrid workers make up only 1–2% of the population, and successful interspecific matings represent approximately 2% of all matings in both species. This shows that, although interspecific matings that give rise to worker offspring occur regularly, they are much rarer than intraspecific matings. Finally, I find no evidence of an association between hybridization and genetic caste determination in this population. Genetic caste determination may be associated with hybridization, but it is not a necessary outcome of it in ants. Although there was no evidence of genetic caste determination, studying this Dorylus system has uncovered the potential for a novel project. After viewing collection data from a collaborator, Caspar Schöning, I hypothesized that Dorylus ants in the subgenus Anomma would constitute a good system for addressing an unanswered question in evolutionary biology: what is the relationship between the permissibility of the genome to introgression between two species and divergence time? Dorylus (Anomma) is a good system for this study because it has multiple species with different areas of allopatry and areas of sympatry with other species in the group. This project would involve sequencing multiple samples of each species from both allopatric and sympatric areas and comparing the genomes of samples from areas of allopatry to those from areas of sympatry to measure the amount of introgression between multiple species pairs. A model is then fit to a plot of the amount of introgression versus divergence time to determine the shape of the relationship
Kronauer, D. Army Ants: Nature’s Ultimate Social Hunters
Daniel Kronauer. Army Ants: Nature’s Ultimate Social Hunters
A swarm raid is one of nature’s great spectacles. In tropical rainforests around the world, army ants march in groups by the thousands to overwhelm large solitary invertebrates, along with nests of termites, wasps, and other ants. They kill and dismember their prey and carry it back to their nest, where their hungry brood devours it. They are the ultimate social hunters, demonstrating the most fascinating collective behavior. In Army Ants, we see how these insects play a crucial role in promoting and sustaining the biodiversity of tropical ecosystems. The ants help keep prey communities in check while also providing nutrition for other animals. Many species depend on army ants for survival, including a multitude of social parasites, swarm-following birds, and flies. And while their hunting behavior, and the rules that govern it, are clearly impressive, army ants display collective behavior in other ways that are no less dazzling. They build living nests, called bivouacs, using their bodies to protect the queen and larvae. The ants can even construct bridges over open space or obstacles by linking to one another using their feet. These incredible feats happen without central coordination. They are the result of local interactions―self-organization that benefits the society at large. Through observations, stories, and stunning images, Daniel Kronauer brings these fascinating creatures to life. Army ants may be small, but their collective intelligence and impact on their environment are anything but.https://digitalcommons.rockefeller.edu/ru-authors/1178/thumbnail.jp
Dissection of Neurons and Circuits Involved in Regulating Innate Behaviors, Movement and Higher Cognitive Functions in Mice
Elucidating the mechanisms through which brain circuits influence behavior is a fundamental tenet of Systems Neuroscience. Advancements in this field are critical to help us understand the inner workings of our brains, and eventually who we are as humans. Describing the physiologic functioning of neural circuits is also necessary to recognize their malfunctions, and to develop strategies to correct them. In many cases, however, alterations in the activity of brainwide circuits can be traced back to specific neuronal populations, and acting selectively upon these cells can restore the normal activity within the system, ultimately correcting the aberrant behavior. Thus, understanding how changes in gene expression and molecular profiles of neurons alter their function is critical to describe interneuronal dynamics within a circuit. During my graduate studies in the Friedman Laboratory at Rockefeller I had the opportunity to combine both Systems and Molecular-Cellular approaches to dissect the circuits and identify the neuronal populations involved in regulating behaviors along the broadest spectrum: from subconscious and innate behaviors (ie, control of energy homeostasis) all the way to the highest order functions (ie, anxiety and compulsive behaviors). To do so, I studied the interaction between cells, circuits and behavior in mice, an ideal model to test these conserved functions. This is because the mouse brain is evolutionarily close to the human brain, yet it is simpler and highly accessible to external manipulations with the molecular biology tools currently at our disposal. The main focus of my graduate work has been to investigate the mechanisms underlying movement control, and regulation of emotions and higher cognitive functions. This project responded to my interest, originated during my medical training, in finding commonalities and differences in neural circuits and functions between brain disorders traditionally classified as pertaining to the sphere of Neurology and Psychiatry. I thus focused on a neural network of nuclei deeply involved in these behaviors, known as the basal ganglia, and in particular on the role of the Subthalamic Nucleus (STN) in Parkinson\u27s Disease and Obsessive-Compulsive Disorder. I identified previously undescribed subpopulations of STN neurons, and tested their role in mediating motor, emotional and cognitive functions in mice, both in normal and pathologic state. This part of my graduate work is detailed in Chapter 1 to 6. The data I present here have important implications for the physiology and pathophysiology of movement and psychiatric disorders, with the potential for enabling further translational studies. In addition to my main study, I was fascinated by the work conducted in the Friedman Laboratory to elucidate the metabolic and nervous mechanisms that regulate energy balance in the body. I therefore collaborated with a postdoctoral fellow in the laboratory and adopted the same experimental approaches to dissect a neural circuit involved in the maintenance of body temperature in mice. The anterior hypothalamus has been the main brain area associated with thermoregulation since the 1950s. With our work, however, we found that a brainstem region known as the Dorsal Raphe Nucleus (DRN), and particularly a subpopulation of DRN neurons, can also respond selectively and powerfully to changes in external stimuli to maintain a constant body temperature. We also showed that this effect is achieved by inducing changes in both thermogenesis and locomotor activity, and mediated via projections to the anterior hypothalamus and to other brain areas known to be involved in thermoregulation. This part of my graduate work is detailed in the Appendix section. Taken together, these experiments reveal a circuit configuration that allows for the robust control of an innate homeostatic response
A Role for Mindbomb 1 in Adenovirus Genome Delivery
The journey from plasma membrane to nuclear pore is a critical step in the lifecycle of DNA viruses, many of which must successfully deposit their genomes into the nucleus for replication. Viral capsids strategically navigate this vast distance (and all subsequent lifecycle steps) through the coordinated hijacking of a number of cellular proteins subsequently termed host factors. Given the virus\u27 dependence on these proteins, host factors therefore represent valuable targets for therapeutic interventions. Still, the identity and function of many of these factors remains unknown. In this body of work, I will detail our own journey from initial identification to comprehensive characterization of one such host factor, Mindbomb 1 (MIB1), in the context of adenovirus infection. Adenoviruses (AdVs) are widespread and highly contagious DNA viruses that can cause severe respiratory illness in children and immune-compromised individuals. An initial genome-wide loss-of-function screen to identify host factors for this virus revealed MIB1, an E3 ubiquitin ligase best known for its role in neurodevelopment, as critical for AdV infectivity. In a series of mechanistic studies centered on the earliest stage of infection, we observed that in the absence of MIB1, viral capsids successfully traffic to the proximity of the nucleus but ultimately fail to deliver their genomes within. AdV infection is dependent on MIB1\u27s primary action as an E3 ubiquitin ligase — to carry out ubiquitination, a posttranslational modification widely capitalized upon by viruses for rapid manipulation of the host environment via altered protein localization, activity or turnover. Our work suggests that in the immediate vicinity of the nucleus, MIB1 may be required for the proteasomal degradation of one or more negative regulators of AdV infection. To identify this relevant MIB1-ubiquitination target, we turned to complementary proteomic approaches to determine proteins proximal to MIB1 upon AdV infection and those differentially ubiquitinated in its presence or absence. Using these unbiased approaches, we corroborated previous reports of MIB1 as a core component of centriollar satellites, dynamic structures localized to the intervening distance between centrosome and nucleus. Furthermore, both proteomic approaches independently pointed to an understudied yet evolutionarily-conserved role for MIB1 in regulating RNP granules and cytoskeleton within the perinuclear environment. Understanding the full relevance of these MIB1-regulated pathways to AdV infection and identifying the specific ubiquitination target responsible will be natural extensions of this work to fully dissect the mechanism of MIB1-mediated viral genome delivery. Together, this work highlights yet another creative way in which viruses recruit host cell machinery to facilitate their replication with the potential to inform the design of new antiviral treatments and emerging adenoviral vector-based therapies
Van Slyke, Donald D.
Donald Van Slyke, circa 1920s
Courtesy of the Rockefeller Archive Center
Van Slyke, Donald D. (1883-1971) was a renowned Dutch American biochemist. He received his BA and Ph.D. degrees in chemistry at the University of Michigan. In 1907 he joined the Rockefeller Institute as an assistant to chemist Phoebus A.T. Levene. In 1914 Van Slyke was appointed chief chemist of the new Rockefeller Institute Hospital. After his retirement from Rockefeller in 1948, Van Slyke continued his research at the newly established Brookhaven National Laboratory. His achievements were recognized with numerous awards and honorary degrees, including the National Medal of Science in 1965. Van Slyke was elected to the U.S. National Academy of Sciences.
See also Discovering a New Amino Acid: Hydroxylysine, The Founding of Clinical Chemistry, and National Academy of Sciences Biographical Memoirs
Years at the Rockefeller Institute: 1907-1948; emeritus 1948-1971https://digitalcommons.rockefeller.edu/faculty-members/1077/thumbnail.jp
Feigenbaum, Mitchell J.
Mitchell Feigenbaum, 1987. Photo by Ingbert Grüttner
Feigenbaum, Mitchell J. (1944-2019) was an American mathematical physicist whose pioneering studies in chaos theory led to the discovery of the Feigenbaum constants. Among his many accomplishments, he was the first to discover that many different physical systems follow a common “periodic doubling” path to chaos, paving the way for the emergence of the discipline known today as chaos theory.
Working with Albert J. Libchaber, a Rockefeller colleague, Feigenbaum showed that this universal behavior occurred in a low-temperature fluid dynamics experiment. For this work, Feigenbaum and Libchaber won the prestigious Wolf Prize in Physics, in 1986. In the mid-1990s, Feigenbaum, working with Torsten N. Wiesel who at the time was the university’s president, was instrumental in establishing Rockefeller’s Center for Studies in Physics and Biology, a groundbreaking cross-disciplinary endeavor that aimed to broaden the scope of discussions at Rockefeller and provide access to contemporary thought in the theoretical sciences.
Feigenbaum was born in Philadelphia and raised in Brooklyn, where his passion for mathematics surfaced early. Fascinated by the family radio, he initially planned to become an electrical engineer; but while completing his bachelor’s degree in electrical engineering at The City College of New York, he became enamored of physics, and instead went on to earn his doctorate in theoretical physics at MIT. Temporary positions at Cornell University and the Virginia Polytechnic Institute were followed by an extended stint at Los Alamos National Laboratory, where he did his early work on chaos. Before coming to Rockefeller as Toyota Professor in 1987, Feigenbaum served as a visiting professor at the University; a visiting member of the Institute for Advanced Study in Princeton, New Jersey; and a professor in the physics department at Cornell.
In addition to the Wolf Prize, Feigenbaum we the recipient of a MacArthur Foundation Award and was a member of the National Academy of Sciences, the American Academy of Arts and Sciences, and the American Physical Society.
Years at The Rockefeller University: 1987-2019https://digitalcommons.rockefeller.edu/faculty-members/1103/thumbnail.jp
Stella Chen, violin, and Renana Gutman, piano
Stella Chen, violin, and Renana Gutman, piano, performed Stravinsky: Suite Italienne for Violin and Piano; Beethoven: Sonata No. 10 in G Major, Op. 96; Brahms: Scherzo in C Minor, WoO 2, from F-A-E Sonata for Violin and Piano; Chausson: Poème; Schumann: Intermezzo in F Major from F-A-E-Sonata for Violin and Piano; Wieniawski: Polonaise de concert, Op.4.https://digitalcommons.rockefeller.edu/tri-institutional-noon-recitals/1001/thumbnail.jp
Structural and Functional Studies of the Unconventional Proteobacterial Transcription Activator Crl in Complex with the Transcription Machinery
The σS subunit of RNA polymerase (RNAP) is the master regulator of stress responses in many Gram-negative bacteria. This alternative σ factor assembles with the core RNA polymerase to initiate the transcription of genes needed to survive different environmental changes. Crl is a small protein that activates the transcription of σS-dependent genes. In contrast to most transcription activators, Crl does not bind DNA to help recruit RNA polymerase and instead interacts directly with σS. At the outset of my research, little was known about how the binding of Crl to σS leads to transcription activation. It was not clear if in addition to σS, Crl also made specific interactions with core RNAP. Using structural biology, molecular biology, biochemical and biophysical techniques, I gained novel insight into the unusual mechanism of Crl. This research validated and expanded on previous studies delineating the Crl/σS interaction and showed how a previously uncharacterized interaction between Crl and the β\u27 subunit of RNAP is critical for full transcription activation by Crl. This work advances our understanding of an unconventional mode of transcription activation in bacteria that might be more widespread than currently known. Chapter 1 provides background on bacterial transcription, σ factors, aspects of regulation, and closes with an introduction to Crl. Chapter 2 describes an approach that can be used to gain insight into the regulons of transcription factors like Crl. Most of the research in this thesis is presented in Chapter 3, which uses biochemical and biophysical approaches to elucidate how Crl activates transcription. Appendix A presents an attempt to study the surface of Crl that interacts with β\u27. Appendix B, briefly shows an attempt to investigate an additional mechanism by which Crl can activate transcription
Oral Mucosal Associated Lymphoid Tissue
Slide 3-1: Oral mucosal-associated lymphoid tissuehttps://digitalcommons.rockefeller.edu/immunodeficiency-disease/1000/thumbnail.jp
Selective Targeting of α-DEC-205
Slide 4-12: Selective targeting of α-DEC-205 to CD11c+ dendritic cells in vivohttps://digitalcommons.rockefeller.edu/endocytosis/1011/thumbnail.jp