Biomolecular Condensates in Cancer
Large-scale cytological changes are a classical hallmark of cancer, although the molecular etiology of these changes has historically been poorly understood. A cell can be organized through membrane-bound organelles such as endoplasmic reticulum and Golgi, or through membrane-less biomolecular condensates such as nuclear bodies and stress granules. While membrane-bound organelles are well-studied, the biology of membrane-less biomolecular condensates is less well-understood. It has recently been found that biomolecular condensates form through phase separation - a demixing phenomenon in which the associated macromolecular components form a dense liquid-like assembly. In addition to large well-defined membrane-less organelles, there exist a growing number of examples in which smaller biomolecular condensates mediate key biological processes. Of particular recent interest, much of the transcriptional machinery appears to consist of biomolecular condensates. The meeting is timely since the field of biomolecular condensates in various aspects of biology has grown exponentially in recent years, and the roles of biomolecular condensates in diseases such as cancer are just beginning to be uncovered.
Misregulation of biomolecular condensates is intimately linked to cancer. For example, both PML bodies and the nucleolus are classic membraneless organelles, and both show massive morphological changes in transformed cells, a result that can now be rationalized in terms of changes to the phase behaviour associated with the underlying components. A number of specific cancers are directly linked to proteins we now know can form biomolecular condensates. The FET family proteins are a collection of RNA binding proteins that contain large unstructured low-complexity domains (LCDs). These LCDs are necessary and su cient to drive phase separation, and in a number of different cancers these LCDs translocate to oncogenic DNA binding domains, driving malignancy. A working model suggests the formation of LCD-mediated assemblies at the associated genetic loci recruits transcriptional machinery, driving unfettered gene expression. While the FET proteins lead to malignancy through oncogenes, cancer-associated mutations in the tumor suppressor SPOP disrupt its normal ability to phase separate, demonstrating that both gain-of-function and loss- of-function mutations are possible.
At the level of gene regulation, super-enhancers are biomolecular condensates that occupy specific loci on the genome and drive high-level constitutive transcription. Recent work suggests that super-enhancers form through phase separation, and that their formation at oncogenes may be a common mechanism through which transcriptional upregulation occurs in transformed cells.
Taken together, there is a growing body of work suggesting biomolecular condensates play strong roles in cancer. This is of particular interest from a therapeutic stand-point as previously ‘untreatable’ malignancy should become vulnerable through a better understanding of the molecular basis of their origins. The goal of this timely Forbeck meeting is to bring together cancer-focused medical scientists, biophysicists and cell biologist in an intimate multi- disciplinary environment to generate ideas on how study of this novel eld can lead to novel treatments for cancer.
Venue & Travel Information
5951 Linea Del Cielo
Rancho Santa Fe, Ca 92067
Travel forms are due 30 days prior to the start of the meeting to allow enough time to plan transportation.
The San Diego International Airport (SAN) is the preferred airport as it is only 30 minutes from the meeting location.
- Arrivals - Thursday at 1 PM, 3 PM and 5 PM
- Departures - Sunday at 10 AM, 12 PM and 2 PM
Please familiarize yourself with our policies and procedures for travel. We truly appreciate you taking the time to participate in this meeting. As you make your plans, please remember that we are a nonprofit organization dependent on donations and volunteers. We do NOT pay for upgrades, change fees, incurred costs resulting from a flight change, transportation to or from your local (home side) airport, meals or other incidentals.
- Travel Confirmation will be sent out within 1 week of the meeting. This will include a hotel confirmation number, if there is one, and airport transfer details. We have to wait until we receive almost everyone’s travel to book airport transfer. Due to frequent airline changes, we wait until the week of the meeting to send this out.
- Airport transfer is provided by Foundation staff, volunteers or arranged shuttle at specific times. If you opt to utilize Foundation airport transportation on your travel form, please be patient in receiving this information. We will send it to the week of the meeting.
- Speaker agenda is not sent out prior to the meeting. It will be provided upon arrival in the meeting packet. We do not tell people when they are speaking because we expect everyone to attend all sessions. Sessions are all day Friday and Saturday.
- REMINDER: We do not reimburse for home side airport transfer or incidentals while traveling. We will not honor miscellaneous receipts sent for these expenses.
- Spouses are welcome to come with you at their own cost but are not allowed to attend the meeting. Please no children.
What the Foundation Pays
Accommodations and meals are provided by the foundation during the meeting. Airfare will be covered only if booked through our travel agent. The Foundation will also cover airport transportation on the meeting side at the designated shuttle times. You can select not to utilize Foundation arranged transportation at your own expense when completing the travel form. Once your travel form is received your accommodations and airport transfer will be confirmed. Please let us know of any food allergies or other information we should be aware of on the travel forms.
- If you would like your airfare covered by the Foundation, you must book with our travel agent. Note we do not cover upgrades, changes, late bookings, etc.
- Flights must be booked at least 30 days prior to the meeting to confirm your accommodations and airport transfer.
- As a nonprofit we utilize volunteers and other methods to maximize our efforts (or our donor support) when making accommodations and arranging ground transportation. Ground transportation will be provided upon your arrival either by a foundation volunteer or arranged shuttle. You will be provided airport transportation information the week of the meeting. We do not reimburse for home side airport transfer or incidentals while traveling.
Abstracts are due 30 days prior to the start of the meeting to allow enough time to prepare the meeting book.
The abstracts should be only one or two paragraphs outlining the theme of your presentation and should reflect the objective and spirit of the meeting (see above). Abstracts will be circulated about one week before the meeting. The meeting organizer will start requesting them a month before the meeting.
The meeting structure has been developed over years of experience.
- Participants have approximately 45 minutes, depending on the number of participants, for their presentation and discussion. The presentation is meant as a conversation start and should last about twenty minutes briefly covering background information and areas that are new or need further input. This should be structured in such a way as to lead to a lively discussion. Participants are encouraged to interrupt to ask questions or start discussions.
- A MAXIMUM of 5 slide equivalents per presentation is allowed (Power point slides should not contain more than one graph or gel per slide and no more than 5 bullet points to stress the points being made by the presenter.) We appreciate cooperation with the spirit of this guideline. Handouts are welcome but should be distributed before sessions.
- Everyone is expected to actively participate in every session and discussions.
- The time spent at the meeting is relatively short, so please be familiar with papers received prior to the meeting.
- It is very important that you commit to all sessions of the 2 days of meetings.
Forbeck Scholars Participation
Scholars are selected for each Forbeck Forum. These are outstanding junior clinical or post-doctoral fellows selected based on the quality and relevance of science.
- Scholars present for 30-45 minutes, depending on the number of participants
- The same presentation rules apply for scholars
- After the Forum you are selected to attend, you will attend three years of Scholar Retreats held in Lake Geneva, WI. If you attend a Fall Forum, you will attend the Spring Retreat. If you attend a Spring Forum you will attend a Fall Retreat.
- Scholars are selected by the Foundation Scientific Advisory Board and peer reviewers selected from past Forbeck Scholars.
The outline below illustrates a typical program schedule. You will receive a complete schedule, including speaking times, the Thursday the meeting starts.