PhD Project "Generative genomic sequence-to-function models to design cell type specific regulatory nucleotide sequences" (Sasse, 02) - Heidelberg University

Employer

Centre for Molecular Biology of the University of Heidelberg, Heidelberg University, Heidelberg, Germany

Description

The cis-regulatory code governs when, where, and how much of gene products are created in cells, enabling the formation of various cell types from a single genome. Genomic sequence-to-function models can learn the cis-regulatory language from a large set of genome-wide measurements. Combining these deep sequence-to-function models with generative processes enables us to exploit these model's knowledge to generate new synthetic sequences with specific regulatory functions. However, many different challenges remain in this process, such as model uncertainty outside of training distributions, lacking sequence diversity and variation. A big issue for algorithm development is the lack of experimental feedback. After training on an original data set, subsequent rounds to assess the designed sequences are often inaccessible to computational labs. Yeast is a versatile model organism that allows for high-throughput manipulation and measurement of regulatory elements for fast evaluation of designed sequences. This project will use high-throughput methods in collaboration with the Knop, and the Synthetic DNA accelerator lab to test and refine in silico sequence design methods.

Candidate requirements

We are looking for a highly motivated PhD candidate holding a Master’s in computer science, computational biology, bioinformatics, or similar. A strong background in computational biology, Machine Learning with pytorch or similar deep learning libraries is required.

About the employer

Our junior research group is part of the newly founded CZS Center SynGen (https://www.syn-gen.de/) and the Center for Molecular Biology (Zentrum für Molekulare Biologie Heidelberg, ZMBH, https://www.zmbh.uni-heidelberg.de/) at the renowned Heidelberg University. The CZS Center SynGen is supported by the Carl-Zeiss-Stiftung to promote research and development at the participating Universities in Heidelberg, Karlsruhe and Mainz to develop an internationally visible research focus on Synthetic Genomics. The ZMBH has a long tradition of conducting cutting-edge research in molecular and cell biology, as well as biomedicine. In the years to come, we anticipate rapid advancements and new technologies in the fields of synthetic DNA, artificial intelligence, and all natural sciences. These advancements will collectively drive progress in synthetic and molecular biology, presenting entirely new possibilities for biomedicine, bioengineering, and biomanufacturing. With the CZS Center SynGen Initiative the ZMBH is on a mission to contribute to these developments with fundamental, theoretical or applied research towards programmable biology.

Further details

Our Junior research group develops Deep Genomic Sequence-to-Function (S2F) models to explore how genomic sequences influence gene regulatory functions (More about projects). These highly scalable models integrate various data modalities that measure different aspects of gene regulation in a high-throughput manner. Our research is at the forefront of advancing these models' foundational understanding of gene regulation. We are pursuing three exciting directions: 1) Scaling up current models with single-cell data across diverse species and data types, 2) Incorporating readily available cell type-specific data to train the next generation of cell type-agnostic models, capable of predicting for unseen cell types and conditions, and 3) Developing new generative models to leverage S2F’s foundational knowledge for creating synthetic regulatory elements with tailored properties for biotechnology.

Possible start of employment: Friday, 01 November 2024.

Contract: Full-time, Fixed-term

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