Designing our future
Part of the Technical University of Denmark and DTU Bioengineering, the Digital Biotechnology Lab is a junior research group within the Tropical Pharmacology Lab. We are passionate about harnessing the power of modern technology to innovate the biotechnological landscape and develop real world solutions for the benefit of society. We focus on leveraging the power of data science and automation to discover and understand protein-based binders, such as antibodies, nanobodies, and DARPins. Specifically, we are interested in (1) generating large scale antibody-antigen datasets via phage/yeast display together with next-generation sequencing, which can be used for machine learning, and (2) in silico approaches for the de novo design or affinity maturation of binders. Importantly, this not only allows us to pursue fundamental questions, such as unravelling the core rule set that dictates binder-target interactions, but also translational endeavours, such as discovering cost-effective therapeutics against infectious and neglected tropical diseases (e.g., snakebite envenomings).
FOCUS AREAS
Fundamental
What dictates cross-reactivity of antibodies? Many variables are at play in antibody-target interactions. At the Digital Biotechnology Lab we are trying to understand which ones matter the most, and whether we can use that knowledge to discover more cross-reactive binders. For that purpose, we generate large, multifaceted datasets and employ structural modelling (e.g., AlphaFold2) and de novo design (e.g., RFDesign), as well as mapping the antibody-target interface. With the insights we gain and the data generated in the process we train machine learning algorithms to aid binder discovery and development.
Translational
Monoclonal antibodies have been developed into ‘blockbuster drugs’ and are predicted to reach a market value of 300 billion USD in 2025. Yet, whilst their high specificity and affinity for target antigens make them highly beneficial for many indications, different tools are required when multiple targets need to be neutralised. This is the case with animal venoms that comprise multitudes of similar and dissimilar toxins, but also for mutating diseases, such as cancer and infectious diseases. In such cases, it is beneficial, if not essential, to use broadly-neutralising antibodies that are able to target multiple similar antigens, do not easily lose their efficacy when faced with rapid target mutation, and are easy to manufacture. Thus, at the Digital Biotechnology Lab we use display technologies to discover broadly-neutralising antibodies and antibody alternatives such as DARPins and nanobodies against animal and plant toxins.
Entrepreneurship
At the Digital Biotechnology Lab, we leverage scientific advances to solve the world’s problems. For this reason, significant emphasis is put on evaluating new ideas and findings in an entrepreneurial context. To date, two commercial projects, Sweathut Therapeutics and Immunite, have received soft funding and are being development further.
THE DIGITAL BIOTECHNOLOGY LAB TEAM
Get to Know Us
TIMOTHY P JENKINS
Assistant Professor
Head of Data Science (DTU Bioengineering)
Tim completed his BSc in Zoology & Ecology at the James Cook University in Australia. He subsequently completed his PhD in host-parasite-microbiome interactions at the University of Cambridge and joined DTU as a H.C. Ørsted / Marie Skłodowska-Curie Actions postdoctoral fellow. He was appointed Assistant Professor upon completion of his 2-year postdoc.
THOMAS FRYER
Affiliated Postdoc
Thomas is establishing high-throughput yeast display guided antibody discovery pipelines.
CHRISTOFFER VINTHER SORENSEN
Postdoc
Chris is working on the development of a rapid next-generation sequencing analysis pipeline for in vitro antibody discovery campaigns
Jack Wade
Affiliated Postdoc
Jack is an expert on structural biology and is working on several different in vitro and in silico protein structure projects
DARIAN WOLFF
Industrial PhD student (Novozymes)
Darian will be focusing on discovering and rationally engineering nanobodies against high-value industrial enzymes, as well as characterising their epitope-paratope interface
MAX OVERATH
Alliance PhD student
After completing his MSc at ETH with Sai Reddy, Max is now combining high-throughput in vitro tech with next-generation sequencing and machine learning to tackle snakebite
ASKE UNGER
Affiliated PhD student
As part of his PhD, supervised by José Luis Martinez Ruiz, Aske is conducting a project on automation of antibody characterisation.
William Laprade
Affiliated PhD student
As part of his PhD, William is working on using image AI to identify and quantify different types of venom induced pathologies and has developed both the AHA and NERD tools to provide a cutting edge toolset to the community.
VLAD ROSCA
MSc Thesis
In his special project, Vlad is conducting machine learning guided protein hallucination for de novo therapeutic design
ABRIL DIOSDADO HERNANDEZ
MSc Thesis
Implementation of computational approaches for in silico maturation of existing antibodies against long neurotoxins from snakes.
JANN LEDERGERBER (ETH)
MSc Thesis
In this master project at DTU Bioengineering, Jann will use ML to de novo design antibody mimics for next generation antivenoms using high-end computational tools
![20211226_114607-01[2307]_edited_edited_edited.jpg](https://static.wixstatic.com/media/c60cbc_e12d153565a04f64a827471fc08cbb3e~mv2.jpg/v1/fill/w_460,h_416,al_c,q_80,usm_0.66_1.00_0.01,enc_auto/20211226_114607-01%5B2307%5D_edited_edited_edited.jpg)
CHARLOTTE RISAGER CHRISTENSEN
MSc Special Project
Charlotte's project will investigate the potential of hallucinating CDRH3 sequences against small plant toxins
OLIVER MORELL
BSc Thesis
For his BSc thesis, Oliver is working on Bayesian Optimisation of antibody affinity.
LAURA CHRISTINE ASTRUPGAARD
BSc Thesis
Laura's thesis is focussing on screening for antibody binders to recombinant spider toxins
BRUNA CAVEION
Guest Researcher
Bruna is using her computer science background to establish a tool for the de novo protein hallucination of therapeutics
ALUMNI
ANDREAS SIXTEN HALLSTEIN RYGAARD, BSc
Development of Cross-Reactive Designed Ankyrin Repeat Proteins binders toward Phospholipases A2 for Recombinant Snake Antivenom
EMILIE MARIA SØLLING HENRIKSEN, MSc
Phage display guided discovery of designed ankyrin repeat proteins against Indian snake venom toxins
![20211226_114607-01[2307]_edited_edited_edited.jpg](https://static.wixstatic.com/media/c60cbc_e12d153565a04f64a827471fc08cbb3e~mv2.jpg/v1/fill/w_163,h_147,al_c,q_80,usm_0.66_1.00_0.01,enc_auto/20211226_114607-01%5B2307%5D_edited_edited_edited.jpg)
CHARLOTTE RISAGER CHRISTENSEN, BSc
Phage display guided discovery of designed ankyrin repeat proteins against a small plant toxin
GÁBOR DÁNYI, MSc
High-throughput synthesis and characterization of single-chain variable fragments for in silico antibody discovery
DARIAN WOLFF, MSc
Unlocking cross-reactivity of antibodies by employing crosslinking mass spectrometry and high-density peptide microarrays
JAMES ROONEY, PhD
During his time at DBL James recombinantly expressed several proteins, with putative antimicrobial activity, identified in the excretory-secretory products from gastrointestinal helminths.
JESPER KILDEMAND, MSc
Jesper was working on a broad sprectrum allergy treatment based on designed allergens.
LAURA ASTRUPGAARD, BSc
Laura used her special project to express recombinant spider toxins
VLAD ROSCA, MSc
In his special project, Vlad conducted machine learning guided protein hallucination for de novo therapeutic design
NILS HOFMANN, BSc
Nils is establishing a high-throughput analysis pipeline for NGS data from phage display during his special project
PEER REVIEWED PUBLICATIONS
2023
2022
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2020
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2020
Monica L. Fernández-Quintero, Anne Ljungars, Franz Waibl, Victor Greiff, Jan Terje Andersen, Torelif T. Gjølberg, Timothy P. Jenkins, Bjørn Gunnar Voldborg, Lise Marie Grav, Sandeep Kumar, Guy Georges, Hubert Kettenberger, Klaus R. Liedl, Peter M. Tessier, John McCafferty & Andreas H. Laustsen. Assessing developability early in the discovery process for novel biologics. mAbs (2023).
Line Ledsgaard, Jack Wade, Timothy P. Jenkins, Kim Boddum, Irina Oganesyan, Julian A. Harrison, Pedro Villar, Rachael A. Leah, Renato Zenobi, Sanne Schoffelen, Bjørn Voldborg, Anne Ljungars, John McCafferty, Bruno Lomonte, José M. Gutiérrez, Andreas H. Laustsen & Aneesh Karatt-Vellatt. Discovery and optimization of a broadly-neutralizing human monoclonal antibody against long-chain α-neurotoxins from snakes. Nat Commun (2023).
Marina Papaiakovou, Natalia Fraija-Fernández, Katherine James, Andrew G. Briscoe, Andie Hall, Timothy P. Jenkins, Julia Dunn, Bruno Levecke, Zeleke Mekonnen, Piet Cools, Stephen R. Doyle, Cinzia Cantacessi, DTJ Littlewood. Evaluation of genome skimming to detect and characterise human and livestock helminths. Parasitol. Int. (2023).
Timothy P. Jenkins, Nicolas Lopez Carranza, Amy Bray, Karim Beguir, Andreas H. Laustsen. Can hackathons unlock a new talent pool from the developing world? Nat Biotechnol (2022).
Timothy P. Jenkins, William Michael Laprade, Andrés Sánchez, Tulika Tulika, Carol O’Brien, Christoffer V. Sørensen, Trenton K. Stewart, Thomas Fryer, Andreas H. Laustsen, José María Gutiérrez. AHA: AI-guided tool for the quantification of venom-induced haemorrhage in mice. Front. Trop. Dis (2022).
Andreas H. Laustsen, Bengt H. Gless, Timothy P. Jenkins, Maria Meyhoff-Madsen, Johanna Bjärtun, Andreas S. Munk, Saioa Oscoz, Julián Fernández, José María Gutiérrez, Bruno Lomonte, Brian Lohse. “In vivo neutralization of Myotoxin II, a phospholipase A2 homolog from Bothrops asper venom, using peptides discovered via phage display technology”. ACS Omega (2022).
Wei-qiao Rao, Konstantinos Kalogeropoulos, Morten E. Allentoft, Shyam Gopalakrishnan, Weining Zhao, Christopher T. Workman, Cecilie Knudsen, Belén Jiménez-Mena, Lorenzo Seneci, Mahsa Mousavi-Derazmahalleh, Timothy P. Jenkins, Si-qi Liu, Andreas H. Laustsen “The rise of genomics in snake venom research: recent advances and future perspectives”. GigaScience (2022), 11.
Esperanza Rivera-de-Torre, Charlotte Rimbault, Anna D. Jensen, Christoffer Sorensen, Timothy P. Jenkins, Natalie Saez, Yoan Duhoo, Celeste Menuet, Lars Ellgaard, Andreas H. Laustsen. “Strategies for heterologous expression and purification of animal venom toxins”. Frontiers in Bioengineering and Biotechnology (2022), 9.
Timothy P. Jenkins, Shirin Ahmadi, Matyas Bittenbinder, Trenton Keith Stewart, Dilber E. Akgun, Melissa Hale, Nafiseh N. Nasrabadi, Darian S. Wolff, Freek J. Vonk, Jeroen Kool, and Andreas H. Laustsen. “Terrestrial venomous animals and the envenomings they cause in the Middle East and North Africa”. PLoS NTD (2021), 15 (12).
Nicolai Rügen, Timothy P. Jenkins, Natalie Wielsch, Heiko Vogel, Benjamin-Florian Hempel, Roderich D. Süssmuth, Stuart Ainsworth, Alejandro Cabezas-Cruz, Andreas Vilcinskas, and Miray Tonk. "Hexapod Assassins’ Potion: Venom Composition and Bioactivity from the Eurasian Assassin Bug Rhynocoris iracundus." Biomedicines 9, no. 7 (2021): 819.
Timothy P. Jenkins, David I. Pritchard, Gary Telford, Radu Tanasescu, Cris S. Constantinescu, and Cinzia Cantacessi. “Longitudinal changes in the gut microbiome of human volunteers with remitting-relapsing multiple sclerosis following experimental infection with the hookworm, Necator americanus”. BMC Biology (2021), 19, 74.
Andreas H. Laustsen, Victor Greiff, Aneesh Karatt-Vellatt, Serge Muyldermans, Timothy P. Jenkins. “Animal immunization, in vitro display technologies, and machine learning for antibody discovery”. Trends in Biotechnology (2021).
Timothy P. Jenkins and Andreas H. Laustsen. “Cost of manufacturing for recombinant snakebite antivenoms”. Frontiers in Bioengineering and Biotechnology (2020), 8.
Timothy P. Jenkins, Kamille E. Krause, Carina Skaarup, Mikael Engmark, Nicholas Casewell, Robert Harrison, Stuart Ainsworth, Bruno Lomonte, Julián Fernández, José María Gutiérrez, Andreas H. Laustsen, and Ole Lund. “An interactive database for the investigation of high-density peptide microarray guided interaction patterns and antivenom cross-reactivity”. PLoS Neglected Tropical Diseases, (2020), 14, 6.
Radu Tanasescu, Christopher R. Tench, Cris S. Constantinescu, Gary Telford, Sonika Singh, Nanci Frakich, David Onion, Dorothee P. Auer, Bruno Gran, Nikos Evangelou, Yasser Falah, Colin Renshaw, Cinzia Cantacessi, Timothy P. Jenkins and David I. Pritchard. “Hookworm Treatment for Relapsing Multiple Sclerosis: A Randomized Double-Blinded Placebo-Controlled Trial”. JAMA Neurolology, (2020), published online.
2023
2023
GRANTS & PRIZES
AIDA Award (MabSilico)
USD 170,000
InnovationFund Industrial PhD
USD 207,000
Otto Monsted Travel Grant (TPJ)
USD 1,000
ERC PoC - Immunite
USD 169,000
Otto Monsted Travel Grant (CRC)
USD 1,000
InnoExplorer Immunite
USD 40,000
DTU PoC - Immunite
USD 68,520
ERC PoC - CAT
USD 169,000
Alliance PhD
USD 210,000
DTU Discovery grant - Immunite
USD 22,250
Novo Scholarship - Darian Wolff
USD 8,500
H.C. Ørsted Fellowship extension
USD 62,500
InnoExplorer - Sweathut Therapeutics
USD 250,000
Hørslev-Fonden
USD 30,000
Otto Monsted - ‘Bright Idea Award’
USD 40,000
DTU Discovery grant - Sweathut Therapeutics
USD 22,250
Brødrene Hartmanns Fond
USD 13,200
H.C. Ørsted Postdoctoral Fellowship
USD 177,300
POPULAR SCIENCE
2022
ScienceNordic
Lorenzo Seneci, Timothy P. Jenkins, Shirin Ahmadi, Christoffer V. Sørensen.
2022
Videnskab
Lorenzo Seneci, Timothy P. Jenkins, Shirin Ahmadi, Christoffer V. Sørensen.
“Hallucinationer og lægemidler: Psykedeliske svampes mange funktioner”
2022
ScienceNordic
Lorenzo Seneci, Timothy P. Jenkins, Shirin Ahmadi, Christoffer V. Sørensen.
“Cell death and vomiting: This happens in your body, if you eat poisonous mushrooms”
2022
Videnskab
Lorenzo Seneci, Timothy P. Jenkins, Shirin Ahmadi, Emilie Henriksen, Christoffer V. Sørensen.
“Celledød og opkast: Det sker i kroppen, hvis du spiser giftige svampe”
2021
Videnskab
Lorenzo Seneci, Timothy P. Jenkins, Christoffer V. Sørensen.
“Ekstremt stor forskel på slangernes gift: Ikke to bid er ens”.
2021
ScienceNordic
Lorenzo Seneci, Timothy P. Jenkins, Christoffer V. Sørensen.
“Extreme variation in snake venom: no two bites are the same”.
2020
ScienceNordic
Anna D. Jensen, Timothy P. Jenkins, Thomas Fryer, Andreas H. Laustsen.
2020
Videnskab
Anna D. Jensen, Timothy P. Jenkins, Thomas Fryer, Andreas H. Laustsen.
“Nanobodies: Gemmer kamelens immunforsvar på en mindre og bedre version af antistoffer?”
2020
The Conversation
Andreas H. Laustsen, Line Ledsgard, and Timothy P. Jenkins
“Finally, snakebite is getting more attention as a tropical health issue”