Julian Naderi announced as Schmidt Science Fellow

The former PhD student from the Denes Hnisz´ lab receives up to two years of funding from the Schmidt Sciences foundation.

As a 2025 Schmidt Science Fellow, Julian Naderi will study a unique protein produced by certain Antarctic fishes that prevents them from freezing at subzero temperatures.

His research project addresses a major problem in organ transplantation: the short viability of transplant organs outside the body, which cannot be frozen. He will characterize how this protein regulates cellular responses to extreme cold and explore its potential application in preserving organs. Through protein engineering, Julian will optimize the protein for enhanced function and facilitated delivery, testing its effectiveness in extending transplant viability – particularly benefitting regions with limited medical infrastructure. Julian will pivot from Biochemistry to Biomedical Engineering

Julian was announced as Schmidt Science Fellow because of his successful contribution to the research of gene expression patterns in Denes Hnisz´ lab. Gene expression patterns make neurons different from other cells. Every cell contains the same genetic information, but not all genes are expressed in every cell. Transcription factors (TFs) guide tissue formation and maintain cell identity by binding DNA sequences, balancing gene activation. Recent insights show TFs form liquid-like droplets, or condensates, to function. Inhibiting or enhancing condensate formation affects activity. TFs bind regulatory DNA like enhancers, with DNA-binding domains and intrinsically disordered regions (IDRs). While TF-binding and activation domains are studied, mechanisms for specific gene expression remain unclear. TF IDRs' amino acid patterns aid in forming transcriptional condensates, influencing TF activity and specificity.

During his PhD studies, Julian Naderi explored how non-linear sequence features in human TF IDRs affect their function in activating target gene expression. He found that aromatic amino acid dispersion in TF IDRs controls an evolutionary trade-off between activity and specificity. He identified human TFs with significant aromatic residue dispersion in their IDRs, resembling imperfect prion-like sequences. Mutating aromatic residues in these TF IDRs reduced transcriptional activity.

Using a proteome-wide IDR prediction approach, he discovered that aromatic dispersion in human TFs is less pronounced compared to other protein groups, indicating suboptimal dispersion. Optimizing this feature in TFs without significant aromatic dispersion enhanced transcriptional activity and promoted liquid-like condensate features in vitro, but led to more promiscuous DNA-binding in cells. These findings suggest an evolutionary role of suboptimal features in transcriptional control and highlight a trade-off between TF activity and specificity.

He found out, that optimizing sequence features of lineage-defining TFs like NGN2, C/EBPα, and MYOD1 improved reprogramming efficiency. He proposes that engineering amino acid features to alter condensation may optimize TF-dependent processes, including cellular reprogramming and cell replacement therapy.

Schmidt Science Fellows is an initiative of Schmidt Sciences, delivered in partnership with the Rhodes Trust. Schmidt Science Fellows was launched in 2017 and brings scientific disciplines together to create novel ways of thinking and develop creative solutions. The 2025 fellows consist of 15 nationalities across North America, Europe, and Asia.   

The program for Schmidt Science Fellows seeks the world’s best emerging scientists who have completed a Ph.D. in natural sciences, computing, engineering, or mathematics and places them in fellowships in a field different from their existing expertise. The program funds a one- or two-year postdoctoral placement and provides a comprehensive Science Leadership Program, creating a community of interdisciplinary leaders.