bioHalosis
Discovery of DNA-Binding Proteins

The objective of bioHalosis is to fill-in a technological gap in Chromatin analysis. Indeed, there is currently no robust methodology to identify proteins that bind to a specific DNA element. bioHalosis is a Contract Research Organization offering custom services to identify proteins that bind to any DNA element-of-interest.

Most diseases result from a defect in gene expression. Our proprietary methodology, IDAP for Identification of DNA Associated Proteins allows proteins involved in local chromatin alterations to be detected, thus providing novel pharmacological targets. IDAP is a robust plasmid pull-down methodology that allows efficient detection of specific proteins of interest due to its extremely low background of unspecific proteins

Two recent success stories illustrate the potential of IDAP

Cancer chemotherapy: A novel mode of action of Temozolomide (TMZ), the only chemotherapeutic drug approved in glioblastoma treatment, was unraveled. We implemented IDAP to investigate the mechanism of action of Temozolomide and discovered that this drug is able to induce DNA Double Strand Breaks in the absence of DNA replication. This observation opens avenues for improving the clinical use of TMZ (Fuchs et.al, eLife 2021; Fujii et.al., DNA Repair, 2022).

Trinucleotide repeat (TNR) expansions diseases: There are over 50 developmental, neurological or neuromuscular disorders that result from expansion of trinucleotide repeats. In a recent study, IDAP was used to probe the proteins that bind trinucleotide repeat intermediates formed during repair / replication (Fuchs et.al, DNA 2023). This work represents a proof-of-concept study for the mechanism of expansion of CAG repeats; deep understanding of the underlying mechanism(s) will require additional experiments.

Recently Published papers

Fuchs R.P., Isogawa A., Paulo A. J., Fujii S., Identification of Proteins Specifically Assembled on a Stem-Loop Composed of a CAG Triplet Repeat, DNA (2023) 3, 109–118. https://doi.org/10.3390

Fujii S, Sobol R.W. and Fuchs R.P, Double-strand breaks: when DNA repair events accidentally meet, DNA Repair (2022) doi.org/10.1016/j.dnarep.2022.103303

Fuchs R.P., Isogawa A., Paulo A. J., Onizuka K., Takahashi T., Amunugama R., Duxin J., Fujii S., Crosstalk between repair pathways elicits Double-Strand Breaks in alkylated DNA: implications for the action of temozolomide, eLife (2021) doi.org/10.7554/eLife.69544

Isogawa A., Fuchs R.P. and Fujii S., Versatile and efficient chromatin pull-down methodology based on DNA triple helix formation Scientific Reports (2018) 8:5925 DOI :10.1038/s41598-018-24417-9 https://doi.org/10.1038/s41598-018-24417-9

Proprietary Patent and Know-How

Patent: New method for the isolation of the proteins bound to any kind of interesting nucleic acid sequence. Robert Fuchs and Shingo Fujii, dépot Juillet 2010, brevet européen dépôt n° 10007204.0-2402 ;

Know-how INPI: 1399 Nucleoprotein Washing Procedure (2022) inventors: S. Fujii and Robert P Fuchs; laboratory: MMG (AMU-INSERM-CNRS)