Carla Green

• 1995-1997 Research Assistant Professor, Department of Anatomy and Cell Biology, University of Kansas Medical Center
• 1997-2003 Assistant Professor, Department of Biology, University of Virginia[1]
• 2003-2007 Associate Professor, Department of Biology, University of Virginia [1]
• 2007-2009 Professor, Department of Biology, University of Virginia [1]
• 2009–present Professor, Department of Neuroscience, UT Southwestern [1]

Green is currently a principal investigator in the Department of Neuroscience at the University of Texas Southwestern Medical Center. Her lab studies the molecular mechanism of circadian rhythms in mammals, with a specific interest in the regulatory mechanisms that modulate translational and post-transcriptional processes. The Green Lab is currently focused on understanding the circadian function of Nocturnin, the circadian regulation of metabolism, and the circadian structure and function of Cryptochrome’s core components.

A major focus in the Green lab has been on a protein encoded by the Nocturnin gene, named for its high-level nighttime expression. Nocturnin is a deadenylase thought to be involved in the degradation of mRNA polyA tails, suggesting that it plays a role in post-transcriptional stability and regulation of circadian gene expression, which is most beneficial to the metabolism and ultimately, survival of an organism.[5]

In 1996, Green discovered nocturnin (Noc) in the retinal photoreceptors of Xenopus laevis, where Noc mRNA displayed rhythmic expression in an isolated Xenopus eye in light/dark and constant conditions. They isolated this gene by using a high stringency differential display screen for rhythmic genes in the Xenopus retina. In 2001, Green found Noc homologues in other species such as mice with a high degree coding sequence similarity. Since expanding these studies into mice, they have shown that mouse Nocturnin mRNA is also rhythmic and expressed in many circadian clock-containing tissues. Interestingly, Green's group has shown that though Noc is not directly involved in regulating the master clock gene expression, it is required for oscillator output functions thereby contributing to circadian physiology.[6]

The rhythmic expression of nocturnin (Noc) is seen throughout the body, notably in tissues crucial for metabolism like the liver and intestine. In 2011, Green, Douris, and others were able to show differing Noc phenotypes have emerged implicating involvement of this gene in osteogenesis, lipogenesis, and adipogenesis.[7]

Her lab's current research focuses on identifying Nocturnin's circadian-relevant mRNA targets and understanding how it goes about regulating their expression.[8]

In 2011, Green's lab concluded that transcriptional and post-transcriptional processes are necessary to generate robust circadian rhythms of mRNA expression, but understandings of circadian post-transcriptional mechanisms lag far behind understandings of clock regulation at the transcriptional level. This was found to be due to the lack of well-developed methodologies to find post-transcriptionally regulated genes on a large scale. The authors believe that development of such methods is likely to lead to the discovery of many more genes and mechanisms that are under post-transcriptional control.[9]

Green's findings are cited in more recent developments on post-transcriptional control of the mammalian circadian clock. Recent findings in 2016 inspired by Green's research contribute to post-transcriptional control of human circadian systems in relation to chronomedicine and sleep disorders.[10]

Green's lab has focused heavily on a class of proteins known as cryptochromes, which are blue light receptor proteins found in both plants and animals. Cryptochrome proteins are essential for the proper functioning of the circadian clock in insects and mammals, and for proper development in plants.[11] Cryptoproteins regulate the circadian clocks of plants, insects, and mammals in different ways. Green has worked extensively with an amphibian, the African clawed frog (or Xenopus laevis), as well as mammalian CRY1 and CRY2, to try and uncover the mysteries of these essential transcriptional repressors.[12]

Green's research on cryptochromes began in 2003, when she and colleagues investigated the role of cryptochrome in suppressing the activation of other circadian clock genes such as CLOCK and BMAL1. They revealed that the deletion of Cryptochrome's C-terminal domain resulted in proteins unable to suppress activation of these genes. This result indicates that the C-terminal is not the domain of suppression of CLOCK/BMAL1, but is essential only for nuclear localization.[13][14]

Green has also studied the relationship between the suprachiasmatic nucleus and peripheral circadian oscillators, in which cryptochrome plays a key role. The regulatory region of Cry1, for instance, contains a response region for the Glucocorticoid hormone , such that input of this hormone can activate transcription of Cry1. In Cry1/Cry2 null mice, regular feeding at 24 hour intervals can induce circadian expression of many transcripts, especially those related to metabolism. This shows how peripheral oscillators can bypass the usual circadian feedback loops of the central oscillator.[15]

More recently, in 2018, Green contributed to the discovery of a new co-factor which mediates regulation through direct interaction with CLOCK and BMAL1. This study provides a model for the evolutionary mechanism by which the structure of cryptochromes, and thus clock regulatory mechanisms, varies.[16]