Quellos High Throughput Screening Core
Frequently Asked Questions
General Questions
Who can use the Quellos High Throughput Screening Core facility?
Answer
The Quellos High Throughput Screening Core is available to Academic and Non-Academic / Commercial users alike. Clients will find our fees and terms competitive and quite attractive.
If I'm an "Out-of-the-Area" client, what are my options for performing screens at the facility?
Answer
Basically, there are two options for our "Out-of-the-Area" clients:
- Option 1: Being predominantly a "Client-Run" center, users are expected to supply personnel/labor and purchase all disposable lab ware and consumables for their screens. Being located in the Lake Union area of Seattle, the core facility is within walking distance to affordable accomodations and meals.
- Option 2: In limited circumstances, special arrangements can be made whereby the "Full Service" option can be made available. The core's staff will provide all materials and labor (i.e., for a fee) for completion of the client's screen.
What are the fees for screening? Are there mechanisms for offsetting costs? Is the Core's automation equipment available for use on a "time/usage basis"?
Answer
Please visit our website for information concerning fees (www.depts.washington.edu/uwhts/). As indicated, the posted rates for screens are typical estimated facility charges for the indicated projects. Actual facility charges will vary with the screen and are based on the client providing the labor to run the screen. Prior to any work beginning within the facility arrangements must be made for billing. Typically, billing occurs monthly and a PO number is sufficient. A reasonable estimate for the total cost of a screen can be attained by adding another 35% to the estimated facility costs covering consumables. Instrumentation is also available for use on a "cost per time" basis. Investigators are required to receive training prior to signing up for instrument use.
Mechanisms do exist for cost reductions.
Investigators with UW affiliated positions may qualify for a "Quellos Research Acceleration Award". Further details are available online at: www.depts.washington.edu/uwhts/news.php.
Other sources for funding are available as well. Please investigate the following:
Institute of Translational Health Services (ITHS): http://www.iths.org/funding. Select "ITHS Technology and Resource Access Grants" link for more information.
Washington Research Foundation (WRF): http://www.wrfseattle.org/. Contact the Director, Research Commercialization for further information.
Furthermore, due to the sheer volume of disposables and reagents necessary to conduct screening campaigns, quantity discounts are available. Moreover, "exchange for service" arrangements are possible, such as "Sweat/Equity" deals and "Valuation Bartering". Please contact the QHTS Staff for advice consumable purchases and discussion on other such matters.
What initial steps are necessary prior to beginning to screen at the Core facility and how do I gain access?
Answer
We suggest filling out an application and scheduling a discussion with the Core staff. Applications are found on the website and can be submitted electronically. Following application submission, projects are reviewed periodically by the Core's Application Review Committee whereby approval can be granted. Applications are reviewed electronically and project status / comments as indicated by the review committee are sent via email.
What are the functions of the Core's staff?
Answer
The Core's staff is quite experienced in assay development and implementation of high and moderate throughput screens. They can serve as a resource at all stages of a screening campaign. Typically, the staff provides libraries (i.e., small molecule or RNAi) training, consultation and generates screening reports following data analysis. In order to manage screening costs, clients are expected to supply their own consumables (i.e., with staff guidance) and the actual labor. In select instances, our "out of the area" clients can opt for a full service option with negotiable terms.
Just how long does a typical screening campaign take to complete?
Answer
Check back soon…answer(s) is/are being formulated…
In anticipation of screening, how far in advance should I fill out an application and make an appointment with the Core's staff?
Answer
The simple answer is "ASAP". Many of our clients are new to HTS and lack experience with the technology. The actual process of applying will guide and aid the naive investigator inexperienced with screening subtleties. Furthermore, early intervention by the Core's staff can help guide such investigators toward processes that increase the probability of success and ultimately save on time and resources. Those clients with previous HTS experience will benefit by early interaction with the staff to help tailor their project's particular requirements for future screening.
Due to unavoidable circumstances, I will have to screen after normal business hours. Will this be possible?
Answer
UW Medicine at Lake Union is a secure facility with 24hrs surveillance seven days a week. Arrangements are possible whereby after-hour access to the facility can be made available.
I'm a screening novice and what's new to me may not be new to others. Are there others that I can contact with previous experience with screening or with my particular assay?
Answer
Please feel free to contact the core facility staff for advice and contacts that can aid your future use of the facility and HTS technology.
Chemical (Small Molecule) Screening
With regards to chemical libraries and small molecule screening, "who, what, where, when and how"?
Answer
Chemical modulator screening typically involves:
- Assay optimization phase in which parameters such as incubation time, protein amount or cell number, compound / solvent concentration and signal detection are optimized for manageable hit rates.
- Actual screening phase whereby the client has chosen the library to be screened:
- Diversity/Focused Screening: Clients needing small molecule leads for novel targets when little information exists are directed toward the Core's "Informer Screen". This screen covers a broad array of the existing biological pharmacophore space thereby increasing the probability of finding an interacting molecule. In other instances, clients can choose among other pre-plated focused collections such as libraries targeting kinases or Ion channels when more is known of their specific target/system.
- Secondary/"Cherry-picked" Screening: Clients that have completed the "Informer Screen" or have performed screens previously with validated "hits" or have a validated chemical series from the literature can choose this option to create a customized library from the Core facility’s chemical collection following input of their known structures and/or hits.
Core Facility's Chemical (Small Molecule) Library
The primary portion of our small molecule library was acquired from ChemBridge Corporation. Initially, the library contains approximately 114,080 separate entities at 10mM concentration in 100% DMSO. The library arrived and is stored long-term in 96 well plates (80 compounds per plate, 1,426 plates) but has been reformatted into 384 well plates (320 compounds per plate, 357 plates) for screening purposes. The "Informer Screen" is performed on a 50K subset of compounds from the library that represent a broad distribution of chemical/biological space (DIVERSet). Secondary/Focused Screens are performed on a subset of the remaining library (~64K total; CNS-Set, KINASet, ION Channel Set, custom-pick).
The "NCI Diversity Set #1" was derived from a Developmental Therapeutics Program (DTP) at the National Cancer Institute, National Institute of Health. The set contains nearly 2,000 entities derived from the original library of 140,000 compounds created by submission from external investigators worldwide or DTP directed syntheses. This set is predominately utilized in optimization assay runs to aid setting screening parameters prior to performing an actual screen.
The "Approved Oncology Drugs Set", also obtained from the DTP is a set of FDA-approved anticancer drugs to enable cancer research. This plated set (2 microtiter plates/set) contains most current FDA-approved anticancer drugs. The set consists of 88 agents and is intended to enable cancer research, drug discovery and combination drug studies. Details on the drugs included in this plated set can be found on their website: www.dtp.nci.nih.gov/branches/dscb/oncology_drugset_explanation.html. Compounds in this set are all proprietary agents that were obtained through commercial sources. We have reformatted this set into a 384 well plate format in order to enable rapid generation and analyses of the resulting 8 point dose response curves.
Future planned acquisitions for the Quellos High Throughput Screening Core's Chemical Library include:
- Human Experience and Known Bioactive Collections, such as:
- Prestwick Chemical Library:
1,200 small molecules, 100% being marketed drugs in US and Europe.
- Microsource Discovery Spectrum Collection:
2,000 known drugs, experimental bioactives and pure natural products.
- Sigma's LOPAC (Library of Pharmacologically-Active Compounds):
1,280 pharmacologically active compounds
- "Fill-in" compounds for potential holes within the library:
Consultation with trained computational/medicinal chemist planned…
Targeting on the order of 10k to 50k additional compounds
I've done the screen and secondary assays. How can I obtain another sample of my hit(s)?
Answer
As part of the small molecule screening program, the core will provide clients a small aliquot of the mutually agreed upon hit(s) for further testing within the clients laboratory. Furthermore, re-stocking information is available to clients to facilitate their purchases from the manufacturer. Access codes will be provided allowing discounts for any restocking purchases.
RNA Interference Screening (RNAi, Loss of Function)
With regards to "RNA Interference" screening (loss of function, siRNA, etc.), "who, what, where, when and how"?
Answer
Check back soon…answer(s) is/are being formulated…
Equipment/Materials/Training
What does the Core facility provide?
Answer
Check back soon…answer(s) is/are being formulated…
What do I need to purchase? And how much will it cost?
Answer
Check back soon…answer(s) is/are being formulated…
Aren't all 96/384 well plates the same?
Answer
Not all 96/384 multi-well plates and reservoirs are the same size or manufactured with the same precise specifications from "batch to batch" or "manufacturer to manufacturer". Even plates manufactured to the SBS standard, (i.e., Society of Biomolecular Sciences automation approved specifications; this standard defines the dimensional requirements of the height and other dimensions of a microplate as specified in American National Standards covering these microplates), can have difficulty in plate handling and within stackers. A dropped or misaligned plate can have catastrophic effects on a given day's screening with loss of time and precious materials. Before placing any orders for disposable labware and reagents, please be sure to check in with a QHTS representative for sign-off and recommendations. We wish for nothing more than your screening campaign's effortless success and the acquisition of quality data.
What equipment is available for screening and how do I choose? Will I be able to receive formal training?
Answer
The QHTS Staff will guide you
Miscellaneous
Do Core Staff members wish to be placed on and funded by my Grant? Does the Core facility issue letters of support?
Answer
Members of the QHTS Staff do not need to be placed on grants. However, we do write "letters of support" for clients that are submitting grants with screening intentions. Do contact the Staff for further details.
How should I acknowledge the Quellos High Throughput Screening Core in publications?
Answer
The Core Facility can be referenced as:
Quellos High Throughput Screening Core, Institute for Stem Cell and Regenerative Medicine, UW Medicine .
Individual staff members can be referenced as deemed appropriate. Please check with the staff for feedback prior to submission…
Should the sources for the chemical/biological screening materials be specified?
Answer
Yes, sources of screening materials should be indicated in publications. Please contact the Core Facility Staff for details related to libraries and other materials used in your screen.
With regards to screening within the facility, who does the information/data belong too? Do I as a client have freedom to operate with the "hits" obtained from screening at the Core facility? How does your Core differ from the NIH MLPCN in this regard?
Answer
The answer to questions related to "Ownership" of data and "Freedom to Operate" is covered within the Core's HTS Master Services Agreement. The "Short & Sweet" answer is that it was the intent of the founders of the Quellos High Throughput Screening Core that the "Client" retains the rights to the data and information that their screening project generated. Any Client's "Freedom to Operate" is governed by agreement(s) they may have established with their sponsoring body, be it via institutional grant funding or the rights of an employer from an academic university/institution or commercial entity.
Although in theory, this philosophy doesn't appear to contrast with agreements governing screening at the NIH Molecular Libraries Probe Production Centers Network (MLPCN), the actual practice differs significantly with regards to timing. Closer inspection of the data sharing and intellectual property policies of the NIH MLPCN indicates that compliance requires public reporting of screening results after a 6 month delay once hits are validated. Exceptions to this rule can tack-on an additional 90 days. Although 6-9 months may seem to be plenty of time to analyze hits and perform secondary assays, in practice, such a delay in dissemination of screening data is far too short for typical intellectual property protection afforded by industry standard practices. The philosophy adopted by the Quellos High Throughput Screening Core lets the Client decide on whether to make such information publically available and when to disclose such data. We feel that this policy is in the best interest of our Clients.
