Our Projects

Circadian Rhythms:

1. In collaboration with the group of Annika Guse, COS, University of Heidelberg (https://guselab.de), we are studying photoreceptors, light-regulated gene expression and the circadian clock in coral. These fascinating animals inhabit an extreme environment: shallow, oligotrophic marine habitats and they have evolved endosymbiotic relationships with photosynthetic dinoflagellates. In order to ensure high levels of photosynthesis in the endosymbionts, coral need to be exposed to high levels of sunlight and so risk increased DNA damage. We have recently documented a surprising diversity of opsin photoreceptors in corals as well as a novel, tandemly duplicated class of cryptochrome proteins that we have termed AnthoCrys1. We have also linked the D-box with the regulation of sunlight induced gene expression in corals suggesting that the sunlight-responsive D-box function represents an ancient evolutionary adaptation1.

2. In collaboration with the laboratories of Cristiano Bertolucci and Tyrone Lucon Xiccato (http://sveb.unife.it/it/ricerca-1/laboratori/behavioural-biology/bertolucci) at the University of Ferrara, Italy, Felix Loosli (IBCS-BIP, KIT) and Jochen Wittbrodt (COS, Heidelberg) (https://www.cos.uni-heidelberg.de/index.php/j.wittbrodt?l=_e), we are characterizing the circadian timing system in medaka. As well as providing a powerful set of genetic tools for detailed in vivo functional studies, this species is photoperiodic. Namely, day length has a profound effect on many aspects of its physiology (e.g. medaka are seasonal breeder, only laying eggs during the long days of spring and summer. They therefore represent a powerful model for studying how animals detect and respond to changes in day length. Our studies involve both behavioural and molecular studies2.

3. In collaboration with the laboratory of Prof. Han Wang at Soochow University in China, as part of a DFG / NSFC jointly funded project, we are systematically studying the function of the family of bZip PAR and Nfil3 transcription factors that are able bind to D-box enhancers and thereby regulated transcription in response to sunlight exposure. We use advanced transgenic and CRISPR based knock out zebrafish models as well as the cavefish P.andruzzii which shows natural loss-of-function mutations in the D-box regulatory pathway. Our goal is to explore the relative contribution of D-box binding transcription factors to the regulation of the circadian clock and DNA repair systems.

4. In collaboration with the laboratory of Lennart Hilbert (IBCS-BIP) and Ralf Mikut (IAI), we are developing mathematical models for the zebrafish circadian clock. Our goal is to use modelling as a complementary tool to explore the mechanisms underlying the direct regulation of the fish circadian clock by light, and also how mutations have led to a blind clock in cavefish.

5. As part of a long-term collaboration with the laboratory of Prof Yoav Gothilf at the University of Tel Aviv, Israel (https://en-lifesci.tau.ac.il/profile/yoavg) we are studying the tissue specific function of clock proteins in fish. In particular, we are collaborating on the characterization of transgenic fish lines prepared by the Gothilf laboratory, where a dominant negative truncated form of Clock is expressed in specific tissues and thereby leads to tissue specific loss of clock function.

6. In collaboration with the laboratory of Gabriele Gerlach, University of Oldenburg (https://uol.de/biodiv-evo-tiere), we are characterizing the circadian clock mechanism of the clown anemonefish Amphiprion ocellaris. As well as cloning clownfish clock gene homologs, we are exploring their temporal expression pattern during larval and juvenile development as well as in a clownfish-derived cell line that we have established in our laboratory. This represents a first step towards exploring the contribution of the circadian clock to coordinating key steps in the complex life history of this fascinating, iconic species.

7. In collaboration with the laboratory directed by Prof. Viola Calabro´, University in Naples, Italy, (http://www.dipartimentodibiologia.unina.it/personale/viola-calabro/) we are studying the role of YB-1 in DNA-repair mechanisms and its link to inducing chemo-resistance in patients with high levels of YB-1 nuclear protein. With this project we aim to study in detail the mechanism of the circadian regulation of YB-1 and its role in the repair of DNA-damage. Study of the circadian clock regulation of YB-1 in its cytoplasmic function of stress granule formation by light, ROS and UV. Our long-term goal is to achieve a non-invasive manipulation of the nuclear concentration of YB-1 that in turn can result in more efficient chemotherapy. This project is funded by travel funding support by DAAD-MIUR.

1. Gornik, S. G. et al. Photoreceptor diversification accompanies the evolution of Anthozoa. Mol Biol Evol msaa304- (2020) doi:10.1093/molbev/msaa304.

2. Lucon-Xiccato, T., Conti, F., Loosli, F., Foulkes, N. S. & Bertolucci, C. Development of Open-Field Behaviour in the Medaka, Oryzias latipes. Biology 9, 389 (2020).

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