Circulating tRNA-derived fragments as biomarkers and therapeutic targets in schizophrenia

Background and rationale

tRNA-derived fragments (tRFs) are abundant small non-coding RNAs in blood and brain that regulate translation, stress responses, and immune signaling. Despite their abundance, tRFs remain unexplored as circulating biomarkers in schizophrenia (SCZ). Recent evidence shows that small ncRNAs play causal roles in synaptic dysfunction and cognitive impairment, making tRFs promising candidates for mechanistic discovery and clinical translation.

Our expertise and resources

Our group at the Institute of Physiology, Czech Academy of Sciences (Prague), specializes in small ncRNA biology in psychiatric and neurodegenerative disease. We have:

• Established bioinformatics pipelines for tRF detection, quantification, and functional analysis

• Published work linking miRNA pathways to synaptic engulfment in SCZ (Kaurani et al., 2024, EMBO)

• Access to the PsyCourse cohort: small RNA-seq from whole blood of SCZ patients and controls

• Detailed clinical phenotypes including cognition (TMT, Digit Span, intelligence), psychopathology (PANSS), and early-life stress measures

• Preliminary data showing differential tRF expression in postmortem SCZ prefrontal cortex

Project objectives

1. Define the circulating tRF landscape in SCZ versus controls using tRF-aware annotation and differential expression analysis

2. Link tRF signatures to cognitive performance, symptom severity, illness duration, and early-life stress exposure

3. Integrate tRFs with miRNA and mRNA networks to infer regulatory pathways affecting synaptic plasticity and neuroimmune signaling

4. Functionally validate top tRF candidates using reporter assays and cellular models (neurons, microglia)

What we bring to a consortium

• Bioinformatics expertise: small ncRNA analysis, multi-omics integration, network inference

• Experimental models: neuronal and microglial cultures, functional validation assays

• Clinical data: well-phenotyped patient cohorts with multi-dimensional clinical metadata

• Track record: grant experience and high-impact publications

While our core expertise is in tRF biology, our bioinformatics pipelines and experimental platforms are adaptable to other small and large ncRNA classes (miRNA, piRNA, circRNA, lncRNA), enabling integration into broader ncRNA-focused consortia.

Partners sought

We are seeking to join a consortium led by an experienced coordinator with complementary partners having expertise in:

• Clinical psychiatry and patient recruitment for validation cohorts

• Advanced omics technologies (spatial transcriptomics, single-cell RNA-seq)

• Biomarker validation and clinical implementation

• Drug development or therapeutic modulation of ncRNAs

• Health economics and precision psychiatry approaches

We are particularly interested in consortia exploring small ncRNA mechanisms in brain disorders, including but not limited to tRF-focused projects.