Genetic dissection of aggression in Drosophila melanogaster

Aggression is conserved among a large number of animal species, which allows animals to compete for food, mate and defend their territories. Aggressive behaviours can occur between two individuals within the same species. In social species such as ants, chimpanzees and humans, aggressive behaviours can also be displayed between different groups within the same species. While natural aggressiveness is important for survival and reproduction, abnormal aggressiveness can cause the waste of energy and severe injuries. In humans, escalated aggression may lead to wars and genocide. My PhD work utilizes Drosophila melanogaster as a model to study the mechanisms underlying the control of aggression. Two avenues of research have been conducted. Firstly, I investigated the role of vision in the control of aggression. Visual circuit activity was manipulated to examine the effects on aggressiveness in isolated and grouped male flies. My results show that acute loss of vision, but not chronic loss of vision, increases aggressiveness. My results also indicate that unlike olfactory information, vision is not required for social suppression of aggression. The second avenue of my research focuses on understanding genetic basis of aggression. By screening for mutations that affect aggressiveness, I identified the peacefulness (pfs) gene as a novel regulator of aggression. pfs encodes for the conserved molybdenum cofactor (MoCo) synthesis 1 protein (Mocs1), which catalyzes the first step in the MoCo biosynthesis pathway. My results, together with that inhibition of MoCo-dependent enzymes displays antiaggressive effects in humans, support that the control of aggression by Pfs-dependent MoCo pathways is conserved throughout evolution. Thus, targeting Pfs/Mocs1 may help the developmentof new therapeutic approaches to treat patients with escalated aggression.L'agression est un comportement conservé chez un grand nombre d'espèces animales etqui permet à un individu de lutter pour se nourrir, s'accoupler ou défendre son territoire. Le comportement d'agression peut se produire entre individus d'une même espèce. Chez les espèce sociale telle que la fourmi, le chimpanzé et l'Homme, le comportement d'agression peut également se produire entre différents groupes d'individus. Bien que l'agressivité naturelle soit importante pour les processus de survie et de reproduction, une agressivité anormale peut conduire à une déperdition d'énergie et à des blessures sévères. Chez l'Homme, une escalade de l'agressivité peut notamment conduire à des guerres et génocides. Mon travail de thèse utilise la Drosophila melanogaster comme modèle d'étude des mécanismes impliqué dans le contrôle de l'agression. Au cours de mon doctorat, deux axes de recherches ont été développés. Dans un premier temps, je me suis intéressé au rôle de la vision dans le contrôle de l'agression. Pour cela, l'activité du circuit visuel a été manipulée afin de déterminer ses effets sur l'agressivité chez des mouches mâles seuls ou en groupes. Mes résultats démontrent qu'une perte aiguë, mais non chronique, de la vision diminue l'agressivité et ils indiquent également que contrairement aux informations olfactives, la vision n'est pas impliquée dans la suppression de l'agression sociale. Le second axe de ma recherche porte sur l'étude des bases génétiques de l'agression. Via le criblage de mutations pouvant affecter l'agressivité, j'ai pu identifier le gène peacefulness (pfs) comme étant un nouveau modulateur de l'agression. Le gène pfs code pour la conservée Molybdenum cofactor synthesis 1 protein (Mocs1), une enzyme catalysant la première étape de la voie de biosynthèse du cofacteur à molybdène (MoCo). Mes résultats, en accord avec l'observation d'effets anti-agressivité chez l'Homme induits par l'inhibition des enzymes MoCo-dépendantes, supportent l'idée que le contrôle de l'agression exercé par la voie de signalisation Pfs/MoCo-dépendante est un mécanisme conservé au cours de l'évolution. Ainsi, le ciblage de la voie de signalisation Pfs/Mocs1 pourrait permettre le développement de nouvelles approches thérapeutiques ayant pour but de traiter les patients souffrant d'escalade de l'agressivité

The peacefulness gene promotes aggression in Drosophila

Abstract Natural aggressiveness is commonly observed in all animal species, and is displayed frequently when animals compete for food, territory and mating. Aggression is an innate behaviour, and is influenced by both environmental and genetic factors. However, the genetics of aggression remains largely unclear. In this study, we identify the peacefulness (pfs) gene as a novel player in the control of male-male aggression in Drosophila. Mutations in pfs decreased intermale aggressiveness, but did not affect locomotor activity, olfactory avoidance response and sexual behaviours. pfs encodes for the evolutionarily conserved molybdenum cofactor (MoCo) synthesis 1 protein (Mocs1), which catalyzes the first step in the MoCo biosynthesis pathway. Neuronal-specific knockdown of pfs decreased aggressiveness. By contrast, overexpression of pfs greatly increased aggressiveness. Knocking down Cinnamon (Cin) catalyzing the final step in the MoCo synthesis pathway, caused a pfs-like aggression phenotype. In humans, inhibition of MoCo-dependent enzymes displays anti-aggressive effects. Thus, the control of aggression by Pfs-dependent MoCo pathways may be conserved throughout evolution

Silastic Thickness Optimization in Uveal Melanoma Brachytherapy by Monte Carlo Method

Introduction In order to treat uveal Melanoma , first, radioactive seeds are laid on a silicone- made substance which is called Silastic after that they are inserted in the plaque, and finally, this plaque containing silicone-made substance is stitched to the sclera surface. The dose gradient within the tumor and healthy tissues can be varied due to changing the Silastic thickness between sclera surface and radioactive seeds. In turn, this leads to difference in the amount of absorbed dose of tumor and healthy tissues. Present study is to investigate the optimum Silastic thickness in uveal Melanoma brachytherapy.  Materials and Methods To measure changes of depth dose of the plaque in a sphere with a radius of 12 mm, MCNP4C code was applied. Exact specifications of a 20-mm Collaborative Ocular Melanoma Study (COMS) plaque, Silastic and three I-125 seed sources, 6711 model were integrated in simulation. Dose calculations were performed using F6 tally in spheres with a radius of 0.2 mm. Results By measuring the changes of dose rate of plaque in distances of 0.2 to 18 mm from the sclera surface and having the prescribed dose for the absolute treatment of eye melanoma, final absorbed doses by tumor and healthy tissues for each different Silastic thicknesses of 0, 0.5, 1, 1.5, and 2 were calculated. Conclusion Considering the results and sclera tolerance, it was concluded that the thickness of Silastic must not exceed 0.5 mm, because increasing the Silastic thickness from this area, increases absorbed dose by healthy tissues and also the treatment time