Project acronym RadioClick
Project A versatile ultrafast Click platform for antibody based radio diagnostics
Researcher (PI) Edward Anton LEMKE
Host Institution (HI) JOHANNES GUTENBERG-UNIVERSITAT MAINZ
Call Details Proof of Concept (PoC), ERC-2017-PoC
Summary Diagnosing cancer as early as possible is one of the most powerful strategies in modern medicine to improve
human well-being. Antibodies (Abs) are excellent molecules that can be used to target specific tumors. As Abs
require hours to days for accumulating on tumor surfaces, the use of Abs for nuclear imaging (such as PET
imaging) is limited by the short half-lives of popular radioisotopes. Therefore, we plan to move the step of radiolabeling
from the bench to the tumor itself. However, the entanglement of Abs with an artificial chemical probe is
one of the most promising but at the same time one of the most technically challenging developmental areas in
biotechnology. Our unique approach is based on the production of “hybrid-Abs”, which combine in only one “click”
step the power of synthetic chemistry with the best of biology (“custom-biologics”). Our unique selling points are
ultra-fast, exceptional bioorthogonal and specific labeling reactions in living organism as well as a both-sided
modularity of the connection between Abs and chemical probe. By doing so, high contrast visualization of the
cancer will become possible.
Summary
Diagnosing cancer as early as possible is one of the most powerful strategies in modern medicine to improve
human well-being. Antibodies (Abs) are excellent molecules that can be used to target specific tumors. As Abs
require hours to days for accumulating on tumor surfaces, the use of Abs for nuclear imaging (such as PET
imaging) is limited by the short half-lives of popular radioisotopes. Therefore, we plan to move the step of radiolabeling
from the bench to the tumor itself. However, the entanglement of Abs with an artificial chemical probe is
one of the most promising but at the same time one of the most technically challenging developmental areas in
biotechnology. Our unique approach is based on the production of “hybrid-Abs”, which combine in only one “click”
step the power of synthetic chemistry with the best of biology (“custom-biologics”). Our unique selling points are
ultra-fast, exceptional bioorthogonal and specific labeling reactions in living organism as well as a both-sided
modularity of the connection between Abs and chemical probe. By doing so, high contrast visualization of the
cancer will become possible.
Max ERC Funding
150 000 €
Duration
Start date: 2018-06-01, End date: 2019-11-30
Project acronym SMPFv2.0
Project Next generation single molecule protein fluorescence
Researcher (PI) Edward Anton Lemke
Host Institution (HI) JOHANNES GUTENBERG-UNIVERSITAT MAINZ
Call Details Consolidator Grant (CoG), PE4, ERC-2014-CoG
Summary Fluorescence techniques provide powerful means to study single protein machineries. Single molecule observation of Fluorescence Resonance Energy Transfer (FRET) has become an important tool for probing structure, distances, dynamics, physicochemical properties and size of purified (in vitro) protein complexes. Super-resolution techniques provide complementary spatial information about proteins in live (in vivo) specimen. Although these techniques have become very popular because of their high sensitivity, their throughput is limited by large statistical sampling requirements, complex sample preparation procedures and/or laborious data acquisition workflows. Here, I propose to design a unified single molecule approach by engineering ultrafast, semi-synthetic protein modification techniques and fluorescent readouts into nano/microfluidic hybrid devices. The development of an automated all-in-one Lab-on-a-Chip platform will dramatically improve throughput of single molecule fluorescence techniques. The technology will provide a multiparameter readout of molecular protein mechanisms across time, resolution and complexity scales in a generalised workflow. To demonstrate the power of the new platform, I will apply it to a mechanistic study of the multifunctionality of intrinsically disordered proteins (IDPs), which are vital to cellular function and associated with many disease mechanisms. The polymeric properties of IDPs enable them to populate a variety of states and engage with various cellular binding partners, thus exceeding the sampling limit of existing single molecule technologies. The new method will blur the boundaries between in cell superresolution microscopy and biochemical single molecule studies and unleash the true power of single molecule protein science for a range of applications in analytical sciences, drug discovery, biotechnology, systems biology and fundamental biomedical research.
Summary
Fluorescence techniques provide powerful means to study single protein machineries. Single molecule observation of Fluorescence Resonance Energy Transfer (FRET) has become an important tool for probing structure, distances, dynamics, physicochemical properties and size of purified (in vitro) protein complexes. Super-resolution techniques provide complementary spatial information about proteins in live (in vivo) specimen. Although these techniques have become very popular because of their high sensitivity, their throughput is limited by large statistical sampling requirements, complex sample preparation procedures and/or laborious data acquisition workflows. Here, I propose to design a unified single molecule approach by engineering ultrafast, semi-synthetic protein modification techniques and fluorescent readouts into nano/microfluidic hybrid devices. The development of an automated all-in-one Lab-on-a-Chip platform will dramatically improve throughput of single molecule fluorescence techniques. The technology will provide a multiparameter readout of molecular protein mechanisms across time, resolution and complexity scales in a generalised workflow. To demonstrate the power of the new platform, I will apply it to a mechanistic study of the multifunctionality of intrinsically disordered proteins (IDPs), which are vital to cellular function and associated with many disease mechanisms. The polymeric properties of IDPs enable them to populate a variety of states and engage with various cellular binding partners, thus exceeding the sampling limit of existing single molecule technologies. The new method will blur the boundaries between in cell superresolution microscopy and biochemical single molecule studies and unleash the true power of single molecule protein science for a range of applications in analytical sciences, drug discovery, biotechnology, systems biology and fundamental biomedical research.
Max ERC Funding
1 996 990 €
Duration
Start date: 2015-09-01, End date: 2020-08-31
