Annonce en anglais
Project title: The control of fat metabolism by oppositely acting transcription factors
Type of rotation: M2 Rotation
Supervisor: Andrew Saurin
Concept and Objectives
Altered cellular metabolism is at the core of many complex human diseases. Obesity lies in contrast with such metabolic diseases, as it secondarily and negatively influences the appearance and prognostic of a large number of human pathologies. Obesity is primarily defined by increased adipose fat accumulation. We have recently identified positive and negative transcriptional regulators of fat accumulation in the Drosophila larval fat body, setting conditions for further molecular insights in fat accumulation control. The positive regulator is encoded by the Motif 1 Binding Protein (M1BP) [1] that we recently showed is an essential transcriptional activator of oxidative metabolism during Drosophila development [2]. In the fat body, our transcriptomic data [3] suggest M1BP also controls this essential metabolic process in this tissue, and highlights control of other metabolic paths including pathways linked to lipid metabolism. The negative regulators are encoded by Hox proteins [4], that we initially identified as temporal regulators of autophagy in this tissue [5]. Increasing levels of the Hox proteins or maintaining them after their expression normally ceases, results in the increase of fat accumulation in the larval fat body, mimicking M1BP loss of function.
The M2 project will use state-of-the-art genomics profiling techniques, Drosophila genetics, imaging and molecular biology for studying the antagonistic transcriptional control and dysfunction of fat body lipid metabolism development.
References
- Zouaz, A., et al., The Hox proteins Ubx and AbdA collaborate with the transcription pausing factor M1BP to regulate gene transcription. EMBO J, 2017. 36(19): p. 2887-2906.
- Poliacikova, G., et al., M1BP is an essential transcriptional activator of oxidative metabolism during Drosophila development. Nat Commun, 2023. 14(1): p. 3187.
- Barthez, M., et al., Human ZKSCAN3 and Drosophila M1BP are functionally homologous transcription factors in autophagy regulation. Sci Rep, 2020. 10(1): p. 9653.
- Rezsohazy, R., et al., Cellular and molecular insights into Hox protein action. Development, 2015. 142(7): p. 1212-27.
- Banreti, A., et al., Hox proteins mediate developmental and environmental control of autophagy. Dev Cell, 2014. 28(1): p. 56-69.