Thorsten-Lars Schmidt

Research Focus: DNA-based tools for biophysics and structural biology

Why DNA?

DNA is a unique polymer. It is the information storage molecule of all known life forms, but can also be used to build up complex, artificial structures that are not found in Biology. Our group is leveraging this programmability to engineer nanoscale architectures and tools for applications in Biophysics and Structural Biology. Moreover, we study fundamental mechanical properties of DNA that govern biological processes including transcription, gene regulation and packing in the nucleus.

DNA-Lipid Nanodiscs as Tools for Single-Molecule Cryo-EM of Membrane Proteins

A main focus of our group is to develop molecular tools that allow to study membrane proteins (MPs), which are among the most important, but least understood components of cells. All cells are surrounded by lipid membranes that are almost impermeable for water, salts or nutrients that cells need. For this reason, a large number of membrane protein(MPs) are inserted into the membranes that control cellular functions such as material transport, sensing, intercellular communication, cell adhesion, and energy conversion. MPs are also the targets for many therapeutic drug molecules. Knowledge of the molecular structure of MPs is necessary to understand the underlying molecular mechanisms of their function and can guide the development of therapeutic drugs for many common diseases. However, MPs are difficult to study and therefore the molecular structure of most MPs is still unknown. The goal of this project is to develop broadly applicable new tools using DNA nanotechnology that will facilitate solving MP structures with cryo-electron microscopes. [Nanoscale 2018].

Biophysics of Tightly Bent DNA

The nucleus of a human cell is only few micrometers long, but has to accommodate 2 meters of DNA. For this reason, cellular DNA is compacted in complex ways with DNA-binding proteins such as histones or by supercoiling to accommodate the limited available space. DNA compacting and the resulting high local curvature also plays a role in the regulation of gene expression and to protect DNA from mechanical damage.
Although DNA is arguably the best studied molecule in biophysics, the mechanics and dynamics of tightly bent DNA molecules such as DNA minicircles are not fully understood yet. Our lab combines experimental approaches including atomic force microscopy (AFM) with coarse grained and atomistic molecular dynamics simulations to discover exciting new behaviors of tightly bent DNA and intrinsically curved DNA sequences.

Lab News:

02/26: Soumya and Praneetha successfully defended their PhD theses. I am proud to have worked with you and wish you all the best for your future! 

They also continued the tradition, that every graduate student and Postdoc from my lab (11/11) continued to do research in academia or industry - without any unemployment period. 

Group

Current group members (chronological):

• Sarvinaz Hajiyeva: PhD candidate, Biomedical Sciences PhD Program
• Pranav Srinivasan: Undergraduate research assistant, Physics
• Dr. Fatemeh Fadaei: Postdoc (Biophysics)
• Mark Macri: PhD candidate Physics
• Emma Meyer: Research Assistant (BA Physics)
• Golnaz Golmahammadi: PhD candidate Chemistry (co-supervision with Dr. Goncalves-Schmidt / Chemistry department)
• Anupam Khanal: PhD candidate Physics
• Siavash Fatih: PhD candidate Physics
• Md. Rahidul Shadhon: PhD candidate Physics
• Manisha: PhD candidate Physics
• Noah Aguirre: PhD candidate, Pharmacology PhD program, NEOMED

Alumni, Their Next Career Steps and Current Positions if Known: