Screening for New Circadian Clock Components in Drosophila
Year: 2011
Type: dissertation
Abstract: The endogenous circadian clock adjusts the physiology and behaviour of an\norganism to advantageous periods of the day, and represents an adaptation to daily\nenvironmental cycles, such as light and temperature. Locomotor activity in Drosophila\nmelanogaster represents a robust behavioural rhythm used to study the clock. This\nclock is located in the lateral and dorsal neurons of the fly and in the suprachiasmatic\nnuclei (SCN) of the hypothalamus in the mammal. The molecular bases of underlying\ncircadian timing mechanisms in insects and mammals are conserved. Although we have\na basic knowledge of the Drosophila molecular clock circuits functioning, many\nquestions regarding the nature of the protein complexes that subserve circadian\npacemakers, the connections between the oscillator and the overt rhythms and the\nentrainment signals to the clock remain unanswered.\nTo identify new D. melanogaster circadian components I used three different\napproaches. The first is based on immunoprecipitation of protein complexes using\ntagged CYC, a dedicated clock protein, to pull down its partners. The second employs a\ncomparative approach with the mammalian circadian SCN proteome and the third uses\na tap-tagging design which is used to screen the proteome. Expression studies of\ncandidate proteins, and behavioural analyses using mutants and transgenes to disrupt\nand silence some of these factors, have revealed a number of candidate genes that may\naffect aspects of clock function. Two novel genes involved in glutamate metabolism\nare particularly compelling, and appear to contribute to the circadian mechanism by\nmediating the neurons that are important for light input. A further synaptic gene may be\ninvolved in setting the clock pacemaker.
Author: Renata Van Der Maas de Azevedo
Language: English
Subfield: Endocrine and Autonomic Systems
Field: Neuroscience
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W846313063