Host Labs and Projects
YNSS Scholars will each complete an independent project under the supervision of one or more mentors in a Yale laboratory. A list of available labs and projects is provided below. During the application process, students will be asked to list three laboratories that most interest them and explain why. This will provide the application review committee with a more comprehensive understanding of each student’s interests. However, laboratory placements depend on many factors, and a student may be assigned to a lab that is not one of the three they described in their application.
We strongly encourage applications from populations underrepresented in the sciences, including women, minorities, and individuals with disabilities.
Laboratories and Potential Projects
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Braddock Laboratory
- Recommended Prior Experience: Completion of high school Chemistry and upper-level Biology courses.
- General Lab Description: The Braddock Laboratory studies severe genetic disorders in infants and children. We use murine models of genetic disease to understand disease pathogenesis and seek to address disease pathogenesis by engineering novel biologics. We are currently working on mineralization disorders associated with ENPP1 deficiency, autoimmune disorders associated with DNAse1L3 deficiency, and genetic forms of childhood obesity associated with the rs1044498 SNP.
- Project Description: The specific project plan will depend on the genetic disorder the student is interested in. All projects will involve some degree of phenotyping and characterizing animal models of genetic disease and may also include dosing studies to investigate the efficacy investigational biologic therapy. Additional tasks include the purification of endotoxin free biologics using state-of-the-art biochemical techniques, cell biology for the propagation and production of stable mammalian cell lines, and molecular biology and high throughput assays for the design and screening of biologic therapeutics that can be developed into new treatments.
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DiStasio Laboratory
- Recommended Prior Experience: Coding experience (Python or Java preferred)
- General Lab Description: As part of the Yale Center for Neuroinflammation, the DiStasio lab focuses on diseases of the central nervous system, including immune dysregulation, neurodegeneration, motor system diseases, and cancer. We develop new techniques in computational pathology to better understand and diagnose diseases. This involves the application of machine learning, image analysis, and statistics to histologic, genomic, clinical, and physiologic data. Our overall goal is to better characterize and classify the pathologic populations of central nervous system cells, and their interactions with their local microenvironment, to understand pathways implicated in disease and to uncover new therapeutic targets.
- Project Description: The goal of the project is the determine the spatial locations of macrophages of particular types/states within the human choroid plexus. This will involve analyzing single cell spatial transcriptomic data available in the lab using new techniques under development by lab members. The primary aim will be to determine the location of macrophages with specific signatures relative to epithelial cells and blood vessels.
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Gopal Laboratory
- Recommended Prior Experience: Completion of high school Biology, Chemistry, and Algebra 2
- General Lab Description: The Gopal Laboratory studies cell biological mechanisms underlying neurodegenerative diseases, including Alzheimer’s Disease, frontotemporal dementia, and motor neuron disease (Amyotrophic Lateral Sclerosis [ALS]). ALS is a neurodegenerative disorder characterized by loss of motor neurons, leading to progressive muscle weakness and eventually death. The cellular and molecular mechanisms underlying this disease remains poorly understood, and existing treatments provide only marginal benefits, underscoring the urgent need for more effective therapeutic strategies. Based on human genetics and pathology studies, we now know that defects in RNA processing play a major role in ALS. Pathological aggregation of TDP-43, an essential DNA/RNA-binding protein, is observed in over 95% of ALS cases and is seen in other neurodegenerative disorders. Ongoing projects in the lab are studying how defects in TDP-43 trafficking and RNA processing in nerve cells (neurons) contribute to nerve cell dysfunction in neurodegenerative disease. We are also developing peptide-based inhibitors to combat abnormal protein aggregates in disease.
- Project Description: TDP-43 is involved in RNA processing tasks such as splicing, stabilization, and transport. Mutations in the TARDBP gene, encoding TDP-43, are linked to ALS pathogenesis, highlighting the importance of RNA metabolism in this disorder. Ataxin-2 is another RNA-binding protein which interacts with TDP-43 and influences risk for developing ALS. In the Gopal lab, we have studied the interaction between TDP-43 and Ataxin-2. The overall goal of this YNSS research project is to study whether Ataxin-2 mutations that increase ALS risk are associated with TDP-43 mis localization and loss of function. The student will use immunofluorescence to study the localization of TDP-43 in brain and/or spinal cord tissue from aged Ataxin-2 mutant mice. This project will allow us to understand the functional consequences of Ataxin-2 polyglutamine tract expansions on TDP-43's essential RNA processing roles in neurons. Insights into the roles of TDP-43 and Ataxin-2 offer potential for developing new treatments that target the underlying causes of ALS.
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Libreros Laboratory
- Recommended Prior Experience: Completion of high school Biology and Chemistry classes.
- General Lab Description: The Libreros Laboratory focuses on the cellular, molecular and biochemical mechanisms that govern hematopoiesis and hematopoietic stem fate decisions during the resolution of inflammation and infection. Confocal intravital microscopy is a groundbreaking tool in deciphering the intricacies of the immune system and inflammation within the brain, providing unparalleled insights at the cellular and molecular levels. Our recent acquisition of a cutting-edge confocal microscope allows us to virtually image all major leukocyte subtypes simultaneously in vivo, a technique practiced by only a select few labs globally. Our investigations extend into the realm of clinically relevant mouse models, including the Middle Cerebral Artery Occlusion (MCAO) model, and Escherichia coli (E. coli) infection models—robust translational platforms that closely mirror human conditions and immune-brain interactions during neuroinflammation. Recent compelling evidence has shown that impairment of resolution of inflammation is a crucial pathogenic hallmark in some neurodegenerative disorders.
- Project Description: In bacterial infections such as meningitis or brain abscesses, leukocytes are crucial for containing and eliminating the bacteria. They can cross the blood-brain barrier to reach the site of infection and mount an immune response. We anticipate a combination of advanced microscopy, models of infections, and mediators that control excessive leukocyte action will not only deepen our understanding of immune-brain interactions but also facilitate identification of novel pathways and potential therapeutic targets for neuroinflammatory disorders. The student will perform experiments to determine if resolvins play a role in modulating the inflammatory response and promoting resolution of inflammation in the brain during infections. Understanding the interplay between resolvins, leukocytes, and brain infections is essential for developing new treatments to combat neuroinflammatory diseases and improve patient outcomes.
Mandel-Brehm Laboratory
- Recommended Prior Experience: Completion of high school Biology class.
- General Lab Description: The focus of the Mandel-Brehm Laboratory is to better understand the interactions between the immune system and the brain in wellness and disease. Interactions between the nervous system and immune system are intricate and critical for normal brain function. Aberrant interactions can result in severe consequences, often breaking tolerance to self-proteins and causing autoimmunity, which in turn causes diverse symptoms of behavioral and movement disorders and even psychiatric illness. Despite the allure of studying this intriguing network of cells, involving two different systems, remarkably, little is known regarding how immune cells enter the brain and cause specific regions of neuronal dysfunction.
- Project Description: A major goal of the Mandel-Brehm Lab is to understand how autoimmune disorders attack the brain. There are specific proteins in the brain that are known targets of immune cells such as B cells and T-cells, in different subtypes of autoimmune disease. We hypothesize these proteins have unique functions and localization in the brain that make them susceptible to immune system recognition and attack. The project will measure the levels and location of different proteins that are known targets of antibodies in several subtypes of autoimmune brain disorders. We will test the hypothesis that disease proteins are localized to a very newly appreciated and unique structure in the brain known as the glymphatic system.