Collaborative Research

Academic research

Collaborative Research


QB3 coordinates scientists and resources across multiple UC campuses to tackle major challenges in biomedicine.

QB3 was built to unite scientists, initiate new research directions, and promote collaboration across its three campuses: UC Berkeley, UC Santa Cruz and UCSF. Each campus has strengths, be they life sciences, computation, engineering, or medicine. The QB3 collaborative unit leverages these strengths and resources to build a deeper understanding of complex biological systems and to stimulate the discovery of solutions to societal problems in human health and climate change.

QB3’s collaborative unit, spearheaded by grants coordinator Lise Barbé, leads the conceptualization of innovative ideas, connects research groups that share a common interest in a particular disease area or biomedical tool, and fundraises to enable their groundbreaking ideas that go far beyond what one research group can accomplish. Our first area of focus is neural organoids.

Neural Organoids

Organoids are 3D structures that self-assemble into developmentally relevant cellular models. The promise of neuronal organoids lies in their ability to more accurately model brain development, study neurodevelopmental and neurodegenerative diseases and utilize organoids as a 3D human model in drug screening. However, several roadblocks currently hinder the widespread use of organoids in these applications. Through collaborative research, QB3 aims to address some of these challenges and propel organoids to be more relevant in disease modeling and drug screening.

Vascularized brain organoids to model the blood-brain-barrier and perform drug screening

Brain organoids face limitations in size and cell maturation due to the development of a necrotic core at their center. The incorporation of vascular cells alongside neuronal cells can generate open lumens and vascular channels throughout the organoids. While neurons exhibit increased maturation in the presence of vasculature, the organoid size remains constrained because of the lack of flow, preventing oxygen and nutrients from reaching the core.

Here, we aim to create vascularized brain organoids with flow of nutrients and oxygen throughout the vascular structures. This approach seeks to enhance both the size of the organoids and maturation of neurons. To achieve this, teams specialized in vascularized organoids, multi-lineage organoids and organoids-on-a-chip will work collaboratively. The outcomes of this research are expected to significantly advance the utility of brain organoids in modeling the blood-brain barrier for drug screening and safety studies related to new disease therapeutics.

Aged brain organoids as a model for neurodegenerative diseases

Brain organoids are typically derived from stem cells, where the aging signature is erased during reprogramming. This poses challenges as aging signatures play a crucial role in developing many phenotypes associated with neurodegenerative diseases, such as neurodegeneration. Stem cells, therefore, present difficulties in accurately modeling neurodegenerative diseases.

Therefore, we propose an innovative approach: generating brain organoids from aged cells and incorporating multiple disease-relevant cell types for each model. This strategy aims to unlock in vitro research into disease mechanisms of neurodegenerative diseases, like Alzheimer’s disease, which have proven challenging to model in animals or 2D cell cultures.

Brain organoids as a model for autism and other psychiatric disorders

Autism and other psychiatric disorders are predominantly polygenic, with genetic causes ranging from common mutations to rare variants and de novo mutations. Animal models often fail to replicate the diverse human disease phenotypes observed in autism and psychiatric disorders, and our understanding of in vitro disease phenotypes is limited. To comprehend how different genetic causes can yield similar disease patterns, it is imperative to uncover the functions of these mutated genes.

Brain organoids offer immense potential as models for autism and psychiatric diseases due to their development with multiple cell types and lineages, including neurons, immune cells, and vascular cells. Our approach involves using brain organoids and CRISPR to screen for common disease phenotypes across various mutations. We will integrate these findings with recently discovered dysregulated protein-protein interactions. This combined approach aims to advance our understanding of pathways dysregulated in autism and other psychiatric disorders, ultimately leading to the identification of potential drug targets for therapeutic intervention.