Exploiting the Human Peptidome for Novel Antimicrobial and Anticancer Agents
The goal of CRC 1279 is to discover endogenous human peptides that play key roles in the control of human pathogens and cancers and to optimize them for potential therapeutic applications. To achieve this, the CRC exploits the peptidome, i.e. the entirety of peptides in the human body. This source is of enormous interest because peptides govern numerous physiological and pathological processes. In addition, peptides are key regulators and effectors of innate and adaptive immunity and modulate the survival, growth and metastatic spread of cancer cells. Despite its importance, the human peptidome is functional hardly explored. The main reason for this is its enormous complexity, which makes purification of individual bioactive peptides challenging. In this CRC, we are utilizing comprehensive peptide libraries from human body fluids and tissues for the stepwise purification of endogenous bioactive compounds detected in specific fractions by repeated rounds of functional assays and separation. This approach allows to isolate bioactive peptides from mixtures of up to millions of naturally-occurring compounds. It has proven highly successful and allowed the discovery of numerous as-yet-unknown endogenous agents displaying antimicrobial (i.e. antiviral and antibacterial) and/or anticancer (e.g. antineoplastic and antimetastatic) activity. The framework of expertise and resources available in the CRC allows to define their mode of action and physiological relevance, and to apply state of the art technologies to optimize natural peptides for translational in vivo applications. Notably, a significant portion of endogenous peptides exerts both antimicrobial and antineoplastic activity and could be optimized for therapeutic development. The CRC is highly interdisciplinary and organized in three cooperative research areas that are supported by two essential technology platforms. The first core project generates and provides peptide libraries to the research projects and support them in peptide purification, synthesis, structural analysis and molecular modelling. Projects in area A discovered, characterized and optimized numerous antimicrobial peptides. Projects in area B analyzed the role of endogenous peptides in cancer growth and metastasis, focusing in particular on leukemic and cancer stem cells. In close cooperation with areas A and B, projects in area C develop novel tools and methodologies to optimize the activity, stability and delivery of the bioactive peptides. The CRC is complemented by a technology platform allowing testing of the distribution, tolerability and bioavailability of peptides in animal models. The research consortium opens a new, highly challenging field of research to obtain new insights into the role of endogenous peptides in infectious and oncological processes. It will clarify whether the generation of antimicrobial and antineoplastic peptides from abundant precursors by immune-activated proteases represents a common principle in innate immunity. The ultimate goal is to translate these results into novel peptide-based imaging and delivery tools and therapeutics.
Whats in the news
Double success including a double mechanism
Researchers of CRC 1279 made two interesting discoveries published almost simultaneously in Cell Host and Microbe and Cell on October 14th and 15th, respectively.
Prof. Frank Kirchhoff | September 19th, 2022
CRC 1279 well-represented at the Peptide Therapeutics Forum 2022
Eight members of CRC 1279 participated at the Peptide Therapeutics Forum 2022 of the Swiss Chemical Society at August 25th and 26th in Basel
Prof. Frank Kirchhoff | September 12th, 2022
Science award of the GlaxoSmithKline Foundation for Dr. Konstantin Sparrer
For his studies on how viral pathogens evade immune control, Dr. Konstantin Sparrer received the prestigious 2021 Science Award for Basic Medical Research from the GlaxoSmithKline Foundation.
Prof. Frank Kirchhoff | July 26th, 2022
ERC Advanced Grant for viral traitors
Good news: Prof. Dr. Frank Kirchhoff and his team will receive 2.3 million euros from the European Research Council for uncovering antiviral defense mechanisms.
Dr. Annika Röcker | May 09th, 2022
On the cover: Improving potency and plasma stability of EPI-X4 derivatives
We are happy to announce that our newest cooperative publication made it on the cover page of Bioconjugate Chemistry.
Prof. Frank Kirchhoff & Dr. Mirja Harms | May 04th, 2022
What it takes to cross borders
Members of CRC 1279 show that a single T403R amino acid change allows the Spike protein of the Sarbecovirus RaTG13 to interact with the human SARS-CoV-2 receptor ACE2.
Prof. Frank Kirchhoff & Fabian Zech | December 10th, 2021
Ulm Peptide Researcher participate in Global Health Center for Pandemic Prevention
Members of the CRCR1279 obtained a grant from the DAAD to participate in a Global Health Center for Pandemic Prevention from 2021 to 2025.
Dr. Ludger Ständker | October 10th, 2021
Improving AMPs: Gran1 inhibits Mycobacterium tuberculosis
We evaluated the antimicrobial activity of Gran1 against the major human pathogen Mycobacterium tuberculosis (Mtb) and a panel of clinically relevant non-tuberculous mycobacteria which are notoriously difficult to treat.
By Reiner Noschka | August 10th, 2021
Surprise: SARS-CoV-2 hijacks antiviral factors for efficient infection
IFITMs are well-known to restrict numerous viral pathogens. A new study of CRC 1279 members shows that the opposite is the case for SARS-CoV-2, the coronavirus responsible for the current COVID-19 pandemic.
By Dr. Annika Röcker | July 21th, 2021
First general meeting to prepare for the second funding period
On Monday, June 28th, the first general meeting to prepare for the second funding period of SFB 1279 took place.
June 6th, 2021 | Prof. Frank Kirchhoff
On Friday, May 21st, we received the good news that our CRC1279 is one of 27 CRCs that have been extended.
May 29, 2021 | Prof. Frank Kirchhoff
A nanodiamond-based nanothermometer...
... coated with a polymeric nanogel shell containing the photothermal probe indocyanine green has been designed, which serves as a heat generator and nanoscale temperature sensor. We demonstrate that the intracellular temperature can be inhomogeneous and can even differ by 30 °C. The impact of local temperature changes on cell viability is studied.
April 30, 2021 | 🔗 pubmed
Preventing infection without harming: New antiretroviral peptide discovered in human hemofiltrate
Members of the CRC 1279 identified a peptide that blocks HIV and SIV infection without interfering with the physiological function of the cellular entry cofactor.
by Dr. Annika Röcker | January 21, 2021
The ‘CRC 1279 and beyond’ seminar series goes virtual
We are delighted that the ‘CRC 1279 and beyond’ seminar series is continuing virtually. In fact, two recent interesting virtual seminars have proven that the virtual format still allows exciting scientific discussion.
by Kristina Hopfensperger | January 7, 2021
How to ZAP the coronavirus – a host protein prompts degradation of viral RNA
Upon infection with SARS-CoV-2, human cells produce proteins that restrict viral replication. One of them, called ZAP, has now been characterized by members of the Institute of Molecular Virology.
by Dr. Annika Röcker | October 14, 2020
SARS-CoV-2 Nsp1 blocks protein synthesis and innate immune activation
The novel pandemic Coronavirus SARS-CoV-2 is known to effectively evade human immune defenses. In a close collaboration, the team of Prof. Roland Beckman from the LMU Munich and the labs of Dr. Konstantin Sparrer and Prof. Frank Kirchhoff at the Institute of Molecular Virology, Ulm now revealed the molecular details on how the accessory protein Nsp1 of SARS-CoV-2 shuts down the ribosome and consequently major anti-viral defense systems.
by Dr. Konstantin Sparrer | July 23, 2020
HIV-1 manipulates DNA repair to avoid immune sensing and superinfection
Manipulation of the host cell is essential for replication and spread of HIV-1, the causative agent of AIDS. In a collaborative study, the Wiesmüller and Kirchhoff labs specialized in DNA repair and HIV/AIDS, respectively, now discovered that HIV-1 utilizes its accessory factor Vpu to suppress the accumulation and sensing of nuclear viral DNA species as well as superinfection.
by Prof. Frank Kirchhoff | July 22, 2020
SARS-CoV-2 detected in breast milk
The CRC1279 congratulates Prof. Dr. Jan Münch and his team at the Institute of Molecular Virology Ulm on the first publication of the detection of SARS-CoV-2 in human breast milk 1.
by Kristina Hopfensperger | June 19, 2020
Fighting SARS-CoV-2 – Establishing the basis for future therapeutic strategies
Prof. Dr. Frank Kirchhoff and Jun.-Prof. Dr. Daniel Sauter from the Institute of Molecular Virology receive over 900 000 Euro funding from the Federal Ministry of Education and Research (BMBF) for two new SARS-CoV-2 research projects. Congratulations!
by Kristina Hopfensperger | June 12, 2020
CRC 1279 at the 5th German Pharm-Tox Summit
Congratulations to Maximilian Fellermann who received the young researchers award from the Thieme journal ‘Research’ for the ‘Best Short Presentation 2020 in the subject of Toxicology’.
by Kristina Hopfensperger | March 31, 2020
„Fight nCoV“ – gemeinsam für eine Therapie und Impfung gegen SARS-CoV-2
Die Professoren Jan Münch von der Universität Ulm und Thomas Schrader von der Universität Duisburg-Essen beteiligen sich zusammen mit weiteren europäischen Partnern an dem neuen EU-Projekt „Fight nCoV“. Das Ziel der Forschenden ist es, Wirkstoffe gegen das neue Coronavirus zu testen. Einige vielversprechende Kandidaten sind unter anderem die von Profs. Münch und Schrader entwickelten molekularen Pinzetten.
March 26, 2020 | 🔗 schwaebische.de
The essentials of science communication
The relevance of science communication has been steadily increasing during the last years. The CRC1279 invited Dr. Tobias Maier from the National Institute for Science Communication in Karlsruhe to host a workshop in Ulm.
by Kristina Hopfensperger | March 10, 2020
Introducing the new President of the German Society of Experimental and Clinical Pharmacology and Toxicology: Prof. Dr. Holger Barth
The German Society of Experimental and Clinical Pharmacology and Toxicology (DGPT) nominated CRC1279 member Prof. Dr. Holger Barth to be their president for 2020. Prof. Dr. Barth took over the responsibilities from the outgoing president Prof. Dr. Wieland.
by Kristina Hopfensperger | February 10, 2020
International CRC1279 symposium at Lake Federsee
At the 22nd and 23rd of October over 60 CRC1279 members and several international experts joined the international CRC1279 symposium in Bad Buchau next to the beautiful lake Federsee.
by Kristina Hopfensperger | November 25, 2019
Time to say goodbye… and hello Kristina!
Annika Röcker, so far responsible for Public Relations and Event reports of the CRC homepage, will leave us by the end of March 2019. Luckily, Kristina Hopfensperger will take over.
by Dr. Annika Röcker, Kristina Hopfensperger and Prof. Dr. Frank Kirchhoff
05th of September 2022
CRC 1279 Monday Seminar series with Dr. Michiel van Gent“Intrinsic immune control of human herpesviruses by nonsense-mediated decay“
N27/Online; Time: 15h00
26th of September 2022
CRC 1279 Monday Seminar series with Prof. Holger Barth“Biohybrid transporters for cell-type selective delivery and controlled release of pharmacologically active peptides: Project C02“
N27/Online; Time: 15h00
28th of September 2022
CRC 1279 Monday Seminar series with Prof. Michael Emerman“High throughput CRISPR screens for host factors involved in HIV replication and latency“
N27/Online; Time: 15h00
For more information and previous CRC1279 Monday Seminars klick here