Burglin TR et al. (1992) Nat Genet "New motif in PBX genes."

Burglin TR, Ruvkun GB

[Nat Genet, 1992]

Human pre-B cell acute lymphoblastic leukaemias are associated with a chimaeric gene that is generated from a t(1;19) chromosomal translocation. This fusion joins the regulatory regions of the lymphoid transcription factor gene, E2A, to the C-terminal region, including the homeodomain, of PBX1 (previously called prl). Tow additional human genes (PBX2 and PBX3) with 77-84% identity to PBX1 have been isolated based on sequence similarity. These genes, however, are too closely related to distinguish between recent divergence and conserved essential motifs, if any, outside the homeodomain. Such conserved domains might be revealed by comparing mammalian sequences with those of more evolutionarily distant organisms, such as the expressed sequence tags (ESTs) generated recently in Caenorhabditis elegans.

Skrdla PJ (2005) Biophys Chem "Statistical kinetic approach for modeling lifespan."

Skrdla PJ

[Biophys Chem, 2005]

Lifespan regulation through gene expression involves complex biochemical processes. Unfortunately, current mathematical models for treating lifespan data afford little insight into the mechanisms that control longevity. In this work, we demonstrate the use of a novel kinetic model to successfully fit the lifespan curves of the nematode, Caenorhabditis elegans. Our findings show that population aging may be treated analogously to a dispersive chemical process [P.J. Skrdla, R.T. Robertson., J. Phys. Chem. B 109 10611 (2005)]. Much like the Gompertz model, only two fit parameters, alpha and beta, are needed to adequately describe the entire data set for each nematode population. These parameters relate a ''global first-order time constant'' and a ''global second-order rate constant'', with units of (time) and (time)(-2), respectively. In C. elegans, the increased longevity resulting from DAF-16 (a transcription factor) activity in the intestinal tissue correlates with a larger alpha value and a smaller beta value; the opposite is true for animals with shorter lifespans. A basic physical interpretation of the two parameters is provided.

Hermann A et al. (2015) Curr Biol "A photosensitive degron enables acute light-induced protein degradation in the nervous system."

Hermann A, Gottschalk A, Liewald JF

[Curr Biol, 2015]

Acutely inducing degradation enables studying the function of essential proteins. Available techniques target proteins post-translationally, via ubiquitin or by fusing destabilizing domains (degrons), and in some cases degradation is controllable by small molecules. Yet, they are comparably slow, possibly inducing compensatory changes, and do not allow localized protein depletion. The photosensitizer miniature singlet oxygen generator (miniSOG), fused to proteins of interest, provides fast light-induced protein destruction, e.g. affecting neurotransmission within minutes, but the reactive oxygen species (ROS) generated also affect proteins nearby, causing multifaceted phenotypes. A photosensitive degron (psd), recently developed and characterized in yeast, only targets the protein it is fused to, acting quickly as it is ubiquitin-independent, and the B-LID light-inducible degron was similarly shown to affect protein abundance in zebrafish. We implemented the psd in Caenorhabditis elegans and compared it to miniSOG. The psd effectively caused protein degradation within one hour of low intensity blue light (30 W/mm(2)). Targeting synaptotagmin (SNT-1::tagRFP::psd), required for efficient neurotransmission, reduced locomotion within 15 minutes of illumination and within one hour behavior and miniature postsynaptic currents (mPSCs) were affected almost to the same degree seen in snt-1 mutants. Thus, psd effectively photo-degrades specific proteins, quickly inducing loss-of-function effects without affecting bystander proteins.