Nediljko "Ned" Budisa (; born 21 November 1966) is a Croatian biochemist, professor and holder of the Tier 1

Canada Research Chair Canada Research Chair (CRC) is a title given to certain Canadian university research professors by the Canada Research Chairs Program. Program goals The Canada Research Chair program was established in 2000 as a part of the Government of Canada ...

(CRC) for chemical

synthetic biology Synthetic biology (SynBio) is a multidisciplinary field of science that focuses on living systems and organisms. It applies engineering principles to develop new biological parts, devices, and systems or to redesign existing systems found in nat ...

at the

University of Manitoba The University of Manitoba (U of M, UManitoba, or UM) is a public research university in Winnipeg, Manitoba, Canada. Founded in 1877, it is the first university of Western Canada. Both by total student enrolment and campus area, the University of ...

. As pioneer in the areas of

genetic code Genetic code is a set of rules used by living cell (biology), cells to Translation (biology), translate information encoded within genetic material (DNA or RNA sequences of nucleotide triplets or codons) into proteins. Translation is accomplished ...

engineering and chemical

(

Xenobiology Xenobiology (XB) is a subfield of synthetic biology, the study of synthesizing and manipulating biological devices and systems. The name "xenobiology" derives from the Greek word ''xenos'', which means "stranger, alien". Xenobiology is a form o ...

), his research has a wide range of applications in

biotechnology Biotechnology is a multidisciplinary field that involves the integration of natural sciences and Engineering Science, engineering sciences in order to achieve the application of organisms and parts thereof for products and services. Specialists ...

and

engineering biology Engineering biology is the set of methods for designing, building, and testing engineered biological systems which have been used to manipulate information, construct materials, process chemicals, produce energy, provide food, and help maintain or e ...

in general. Being highly

interdisciplinary Interdisciplinarity or interdisciplinary studies involves the combination of multiple academic disciplines into one activity (e.g., a research project). It draws knowledge from several fields such as sociology, anthropology, psychology, economi ...

, it includes bioorganic and

medical chemistry Medicinal or pharmaceutical chemistry is a scientific discipline at the intersection of chemistry and pharmacy involved with designing and developing pharmaceutical drugs. Medicinal chemistry involves the identification, synthesis and developmen ...

structural biology Structural biology deals with structural analysis of living material (formed, composed of, and/or maintained and refined by living cells) at every level of organization. Early structural biologists throughout the 19th and early 20th centuries we ...

biophysics Biophysics is an interdisciplinary science that applies approaches and methods traditionally used in physics to study biological phenomena. Biophysics covers all scales of biological organization, from molecular to organismic and populations ...

and molecular

as well as

metabolic Metabolism (, from ''metabolē'', "change") is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run cellular processes; the ...

and

biomaterial A biomaterial is a substance that has been Biological engineering, engineered to interact with biological systems for a medical purpose – either a therapeutic (treat, augment, repair, or replace a tissue function of the body) or a Medical diag ...

engineering. He is the author of the only textbook in his research field: “Engineering the genetic code: expanding the amino acid repertoire for the design of novel proteins”.

Early life, education and career

Ned Budisa earned a High school teacher diploma in Chemistry and Biology in 1990, a B.S. in

Molecular Biology Molecular biology is a branch of biology that seeks to understand the molecule, molecular basis of biological activity in and between Cell (biology), cells, including biomolecule, biomolecular synthesis, modification, mechanisms, and interactio ...

and MSc in

Biophysics Biophysics is an interdisciplinary science that applies approaches and methods traditionally used in physics to study biological phenomena. Biophysics covers all scales of biological organization, from molecular to organismic and populations ...

in 1993 from the

University of Zagreb The University of Zagreb (, ) is a public university, public research university in Zagreb, Croatia. It is the largest Croatian university and one of the oldest continuously operating universities in Europe. The University of Zagreb and the Unive ...

. He received a PhD in 1997 from the

Technical University of Munich The Technical University of Munich (TUM or TU Munich; ) is a public research university in Munich, Bavaria, Germany. It specializes in engineering, technology, medicine, and applied and natural sciences. Established in 1868 by King Ludwig II ...

where his thesis advisor was Professor

Robert Huber Robert Huber (; born 20 February 1937) is a German biochemist and Nobel laureate. known for his work crystallizing an intramembrane protein important in photosynthesis and subsequently applying X-ray crystallography to elucidate the protein's st ...

. He also habilitated at the Technical University of Munich in 2005 and worked afterwards as a junior group leader ("Molecular Biotechnology") at the

Max Planck Institute for Biochemistry The Max Planck Institute of Biochemistry (; abbreviated MPIB) is a research institute of the Max Planck Society located in Martinsried, a suburb of Munich. The institute was founded in 1973 by the merger of three formerly independent institutes ...

in Munich. Between 2007 and 2010 he was a member of CIPS^M in Munich. He was appointed as full professor of

biocatalysis Biocatalysis refers to the use of living (biological) systems or their parts to speed up ( catalyze) chemical reactions. In biocatalytic processes, natural catalysts, such as enzymes, perform chemical transformations on organic compounds. Both en ...

at the TU Berlin in 2010 until the end of 2018, when he accepted the Tier 1 CRC position in Chemical Synthetic Biology at the

. Ned Budisa is also a member of the Excellence Cluster ‘Unifying Systems in Catalysis’ (UniSysCat) and keeps

adjunct professor An adjunct professor is a type of academic appointment in higher education who does not work at the establishment full-time. The terms of this appointment and the job security of the tenure vary in different parts of the world, but the term is gen ...

status at the TU Berlin. In 2014, he founded the first Berlin

iGEM The iGEM (International Genetically Engineered Machine) competition is a worldwide synthetic biology competition that was initially aimed at undergraduate and 'overgraduate' university students, but has since expanded to include divisions for hig ...

team.

Research

Ned Budisa applies the Selective Pressure Incorporation (SPI) method that enables single and multiple in vivo incorporations of synthetic (i.e. non-canonical) amino acid analogs in proteins, preferably by sense codon reassignment. His methodology allows for fine chemical manipulations of the amino acid side chains, mainly of

proline Proline (symbol Pro or P) is an organic acid classed as a proteinogenic amino acid (used in the biosynthesis of proteins), although it does not contain the amino group but is rather a secondary amine. The secondary amine nitrogen is in the p ...

tryptophan Tryptophan (symbol Trp or W) is an α-amino acid that is used in the biosynthesis of proteins. Tryptophan contains an α-amino group, an α-carboxylic acid group, and a side chain indole, making it a polar molecule with a non-polar aromat ...

and

methionine Methionine (symbol Met or M) () is an essential amino acid in humans. As the precursor of other non-essential amino acids such as cysteine and taurine, versatile compounds such as SAM-e, and the important antioxidant glutathione, methionine play ...

. These experiments are often assisted with simple metabolic engineering. Ned's research goal is the transfer of various

physicochemical Physical chemistry is the study of macroscopic and microscopic phenomena in chemical systems in terms of the principles, practices, and concepts of physics such as motion, energy, force, time, thermodynamics, quantum chemistry, statistical mecha ...

properties and

bioorthogonal chemistry The term bioorthogonal chemistry refers to any chemical reaction that can occur inside of living systems without interfering with native biochemical processes. The term was coined by Carolyn R. Bertozzi in 2003. Since its introduction, the concept ...

reactions (chemoselective ligations such as

click chemistry Click chemistry is an approach to chemical synthesis that emphasizes efficiency, simplicity, selectivity, and modularity in chemical processes used to join molecular building blocks. It includes both the development and use of "click reactions", a ...

) as well as special spectroscopic features (e.g. blue and golden fluorescence or vibration energy transfer) into the proteins of living cells. In addition, his method allows the delivery of element-specific properties (

fluorine Fluorine is a chemical element; it has Chemical symbol, symbol F and atomic number 9. It is the lightest halogen and exists at Standard temperature and pressure, standard conditions as pale yellow Diatomic molecule, diatomic gas. Fluorine is extre ...

selenium Selenium is a chemical element; it has symbol (chemistry), symbol Se and atomic number 34. It has various physical appearances, including a brick-red powder, a vitreous black solid, and a grey metallic-looking form. It seldom occurs in this elem ...

and

tellurium Tellurium is a chemical element; it has symbol Te and atomic number 52. It is a brittle, mildly toxic, rare, silver-white metalloid. Tellurium is chemically related to selenium and sulfur, all three of which are chalcogens. It is occasionally fou ...

) into the biochemistry of life. Ned Budisa is well known for the establishment of the use of selenium-containing non-canonical amino acids for protein X-ray

crystallography Crystallography is the branch of science devoted to the study of molecular and crystalline structure and properties. The word ''crystallography'' is derived from the Ancient Greek word (; "clear ice, rock-crystal"), and (; "to write"). In J ...

and fluorine-containing analogs for 19F NMR-spectroscopy and protein folding studies. He was the first to demonstrate the use of genetic code engineering as a tool for the creation of therapeutic proteins and ribosomally synthesized peptide-drugs. He has succeeded with innovative engineering of

biomaterials A biomaterial is a substance that has been engineered to interact with biological systems for a medical purpose – either a therapeutic (treat, augment, repair, or replace a tissue function of the body) or a diagnostic one. The corresponding f ...

, in particular photoactivatable mussel-based underwater

adhesives Adhesive, also known as glue, cement, mucilage, or paste, is any non-metallic substance applied to one or both surfaces of two separate items that binds them together and resists their separation. The use of adhesives offers certain advantage ...

. Ned Budisa made seminal contributions to our understanding of the role of

methionine oxidation Methionine sulfoxide is the organic compound with the formula CH3S(O)CH2CH2CH(NH2)CO2H. It is an amino acid that occurs naturally although it is formed post-translationally. Oxidation of the sulfur of methionine results in methionine sulfoxide ...

prion protein The major prion protein (PrP) is encoded in the human body by the ''PRNP'' gene also known as CD230 (cluster of differentiation 230). Expression of the protein is most predominant in the nervous system but occurs in many other tissues throughou ...

aggregation and has discovered the roles of

side chain conformations ( endo-exo isomerism) in

translation Translation is the communication of the semantics, meaning of a #Source and target languages, source-language text by means of an Dynamic and formal equivalence, equivalent #Source and target languages, target-language text. The English la ...

, folding and stability of proteins. Together with his co-worker Vladimir Kubyshkin, the new-to-nature hydrophobic polyproline-II helix

foldamer In chemistry, a foldamer is a discrete chain molecule ( oligomer) that folds into a conformationally ordered state in solution. They are artificial molecules that mimic the ability of proteins, nucleic acids, and polysaccharides to fold into ...

was designed. Along with Budisa's previous work on bioexpression using proline analogues, the results of this project contributed to the establishment of the Alanine World hypothesis. It explains why nature chose the

with "only" 20

canonical The adjective canonical is applied in many contexts to mean 'according to the canon' the standard, rule or primary source that is accepted as authoritative for the body of knowledge or literature in that context. In mathematics, ''canonical exampl ...

amino acids for ribosomal protein synthesis. In 2015, the team led by Ned Budisa reported the successful completion of a long-term evolution experiment that resulted in full, proteome-wide substitution of all 20,899

residues with thienopyrrole-alanine in the

of the bacterium

Escherichia coli ''Escherichia coli'' ( )Wells, J. C. (2000) Longman Pronunciation Dictionary. Harlow ngland Pearson Education Ltd. is a gram-negative, facultative anaerobic, rod-shaped, coliform bacterium of the genus '' Escherichia'' that is commonly fo ...

. This is a solid basis for the evolution of life with alternative building blocks,

s or biochemistries. At the same time, this approach might be an interesting biosafety technology to evolve biocontained synthetic cells equipped with a "genetic firewall" which prevents their survival outside of man-made unnatural environments. Similar experiments with fluorinated

analogs as

xenobiotic A xenobiotic is a chemical substance found within an organism that is not naturally produced or expected to be present within the organism. It can also cover substances that are present in much higher concentrations than are usual. Natural compo ...

compounds (in collaboration with Beate Koksch from the

Free University of Berlin The Free University of Berlin (, often abbreviated as FU Berlin or simply FU) is a public university, public research university in Berlin, Germany. It was founded in West Berlin in 1948 with American support during the early Cold War period a ...

) has led to the discovery of exceptional physiological plasticity in microbial cultures during adaptive laboratory

evolution Evolution is the change in the heritable Phenotypic trait, characteristics of biological populations over successive generations. It occurs when evolutionary processes such as natural selection and genetic drift act on genetic variation, re ...

, making them potential environmentally friendly tools for new

bioremediation Bioremediation broadly refers to any process wherein a biological system (typically bacteria, microalgae, fungi in mycoremediation, and plants in phytoremediation), living or dead, is employed for removing environmental pollutants from air, wate ...

strategies. Ned Budisa is also actively involved in the debate of possible societal, ethical and philosophical impacts of radical genetic code engineering in the context of synthetic cells and

life Life, also known as biota, refers to matter that has biological processes, such as Cell signaling, signaling and self-sustaining processes. It is defined descriptively by the capacity for homeostasis, Structure#Biological, organisation, met ...

as well as technologies derived thereof.

Awards and honors (selection)

* 2004: BioFuture Award * 2017: Publication Award Fluorine Chemistry

References

External links

Homepage of the TU Berlin

UniCat profile

Talk about the future of Xenobiology

Built-in drugs could target tissues

Genetic Code 2.0 – 3 Synthetic Amino Acids Combined Into One Protein

Oxidation sets off fatal structural change of human prion proteins

iGEM.Berlin Magnetic e.Coli

Professor and hobby boxer (article in german)

A Super Adhesive Made from Intestinal Bacteria
{{DEFAULTSORT:Budisa, Nediljko Academic staff of Technische Universität Berlin 20th-century biochemists Croatian biochemists Scientists from Zagreb 21st-century Croatian scientists 1966 births Faculty of Science, University of Zagreb alumni Scientists from Split, Croatia People from Šibenik People from Drniš Living people

Early life, education and career

Research

Awards and honors (selection)

See also

References

External links