BellBrook Labs was awarded a Phase I grant of $225,000 to develop biosensors for detection of chromatin modifying enzymes, such as acetyltransferases and methyltransferases, in collaboration with University of Utah chemist Jennifer Heemstra. The collaboration leverages nucleic aptamer technology being developed by Dr. Heemstra to streamline development of assays for epigenetic enzymes being targeted for cancer and other diseases.
Aptamers as Biosensors for HTS
BellBrook Labs received a Phase I STTR grant of $225,000 from the National Institute of General Medical Sciences for collaboration with University of Utah chemist Jennifer Heemstra to develop high throughput screening (HTS) assays for epigenetic enzymes that cause aberrant gene expression in cancer and other diseases. Dr. Heemstra will use a novel method developed in her laboratory to produce nucleic acid aptamers with special properties that will make it easier for BellBrook scientists to convert them into HTS assays. If successful, the research will relieve a bottleneck in epigenetic drug discovery by accelerating the discovery of inhibitors for histone modifying enzymes such as acetyltransferases and methyltransferases.
Called the “writers” of the epigenetic code, the enzymes that decorate chromatin with chemical groups to regulate gene transcription – most notably methyltransferases and acetyltransferases – are being intensively pursued as targets for development of more effective drugs, especially for cancer. However, these enzymes are difficult to measure in simple, sensitive assays that can be used to discover new small molecule drugs by high throughput screening.
In a separate NIH-funded study, BellBrook scientists recently found a new way to address this problem using a naturally occurring nucleic acid aptamer, or riboswitch, as the basis for a simple, ultrasensitive methyltransferase assay. Unfortunately, nature only makes riboswitches for a limited number of molecules, and developing assays for other types of enzymes such as acetyltransferases will require production of new aptamers. But aptamer development methods are tedious and labor intensive, and it is a risky approach because there is no guarantee that the end products will be suitable for conversion into an HTS assay.
And this is where Dr. Heemstra’s method shows tremendous promise. She has conceived an innovative approach for developing aptamers that not only bind to the desired target, but also can be easily converted into biosensors that produce the fluorescent signals used for HTS assays. Dr. Robert Lowery, BellBrook’s CEO and co-principal investigator on the STTR grant, hopes that by combining Dr. Heemstra’s method with proprietary aptamer signaling technology developed at BellBrook, they can streamline development of HTS assays for epigenetic enzymes and thereby accelerate discovery of new drugs for cancer and other diseases.
Research reported in this publication was supported by the National Institute of General Medical Sciences of the National Institutes of Health under Award Number R41GM121123. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.