Constructor University Bremen gGmbH
Campus Ring 1 | 28759 Bremen | Germany
Dr. Fernandez Lahore is Professor of Biochemical Engineering at the Department of Life Sciences & Chemistry at Jacobs University Bremen. His laboratory runs diverse projects in the fields of bioprocess engineering, enzyme technology / biocatalysis, and bioproduct downstream processing. In addition to offering regular courses serving our undergraduate students (Pharmaceutical Technology, Biorefining), Prof. Fernandez Lahore also teaches a very popular course – “Biotechnology: From Science to Business”.
Current projects under development in Prof. Fernandez Lahore’s Lab are related to:
- Bio production platforms based on filamentous fungi
- Design of novel materials for bioproduct downstream processing
- Bioprocess intensification
- Biochemical synthesis of APIs
- Biorefining of agricultural and forest byproducts
This work has been, and continues to be, funded by public and private agencies, including the DFG, BMBF, European Commission, and private foundation. The Lab has been specializing in actions supporting SMEs across Europe, applied R&D (mainly in cooperation with industrial partners), and translational science in the field of biotechnology. Many projects are coordinated by Prof. Fernandez Lahore from Jacobs University.
Integration and Intensification in DSP:
- Second generation expanded bed adsorption (e.g. biomass effects, affinity capture, novel particles).
- Membrane adsorbents (e.g. material chemistry, ligand design)
- Aqueous two-phase extraction (e.g. reactive extraction)
- Recombinant protein production
- 2D gel electrophoresis, HPLC and mass spectrometry
DSP of natural compounds:
- Food additives (e.g. colorant, stabilizing additives, flavors)
- Pharmaceuticals (e.g. active compounds)
- Enzymes (e.g. aspartic proteinase)
Process modeling, simulation, design and Scale-up:
- Delivering products for biotechnology on the fast track.
- Diploma in Biochemistry, University of Buenos Aires (1986)
- Diploma in Industrial Pharmacy and Biochemistry, University of Buenos Aires (1993)
- Dr. in Industrial Microbiology and Biotechnology, University of Buenos Aires (1995)
- Prize "School of Pharmacy and Biochemistry", University of Buenos Aires (1996)
- "Rene Hugo Thalmann" Fellowship, University of Buenos Aires (1996)
- Postdoctoral Fellowship, National Research Council (Argentina) (1997-1999)
- Member of the program "Return of Talents" (CIM/ZAV - BMZ) (2000-2002)
- Postdoctoral Scientist, University of Düsseldorf in the Research Centre Jülich (1997-2000)
- Member of the National Research Council for Science and Technology (Argentina) (since 2000)
- Associate Professor for Biochemical Engineering (Downstream Processing), IUB (since 2003)
Modern biotechnology heavily depends on the availability of efficient processes, which should be able to generate competitive products (or services) in terms of quality and cost. A critical assessment of current bioprocess technology will reveal that fermentation procedures are already in a phase of technological maturity and that many successful approaches to heterologous protein expression are being employed. However, product recovery and purification (also referred as downstream processing) still poses a number of important challenges. For example, downstream operations cost usually represents more than 50-80% of the total processing cost. Thus, it comes as no surprise that optimisation of the later steps is considered a central element in appropriate bioprocess design. Unfortunately, and probably due to the common practice of expressing proteins at laboratory scale without any concern on how the product will be purified at a larger scale, downstream processing strategies are usually neglected until a later phase of process development. This is a major reason for increased processing cost and eventually the reason for product failure in the market (Datar and Rosen, 1990).
The picture described above has fostered the integration between unit operations devoted to product recovery and purification. The mentioned concept materialises through the introduction of newly designed downstream process technologies which replaces a number of more traditional unit operations, like precipitation, centrifugation/filtration, and column chromatography among others. Efforts to perform integrative purification have been made using aqueous two-phase partitioning, membrane adsorbents or fluidised materials for protein capture (Brandt et al., 1988; Kula, 1990; Hjorth, 1997). Moreover, bioprocess integration is a term also used to describe the need to couple properly upstream and downstream operations, something that quite often is left to chance with dramatic consequences (Wielen and Luyben, 1992).
Within the scope of this project, a meta-integration strategy (refer to Fig. 1.) is proposed by full cross-optimisation from gene to product. The prefix meta- is thus "used with the name of a discipline to designate a new but related discipline designed to deal critically with the original one" (Webster Dictionary). As oppose to the standard practice we will start choosing the downstream operation. This will be an adsorption step based on the well known principle of ion exchange (IEX). Chromatography (or the simpler finite batch adsorption) on anion or cation exchangers is a widespread technique for large-scale protein purification, because of economy, robustness and suitability for cleaning in place (CIP) and/or sanitisation in place (SIP). However, ion exchange is usually regarded as a low-to-moderate-resolution purification step. It also requires concentrations of the target species above a certain threshold in order to effectively bind them (Skidmore et al., 1990). On the other hand, we should remember that packed-bed adsorption does not tolerate the presence of particles in the feedstock thus imposing the need for extensive clarification to avoid system clogging and concomitant back-pressure development (Thömmes, 1997). It is clear that a well designed integrative procedure will attempt to simultaneous solid-liquid separation, product selective isolation and de-watering (target concentration). All those potential drawbacks of the chosen core technology (i.e., IEX) are overcome by taking action towards full cross-optimisation of the whole process: a) Use of gene technology to facilitate product purification, i.e. alteration of protein isoelectric point (pI) by addition of charged amino acid residues; b) Selection of the right system with potential to achieve high levels of foreign gene expression, i.e. the baculovirus expression vector system (BEVS); c) Insect cell cultivation in bioreactor(s) for mass protein production, i.e. Stirred Tank vs. Airlift reactors; and d) IEX system, i.e. adsorption on modified hollow fiber membranes vs. adsorption on fluidised and classified matrices.
|2012-2017||“Gaining Productivity, Cost Efficiency and Sustainability in the Downstreaming Processing of Bio Products by novel Integration and Intensification strategies (INTENSO)”. Funded by FP7-KBBE (EU’s Seventh Framework Programme (FP7); European knowledge-based bio-economy (KBBE)).|
|2012-2016||“Bioprocess Platform for the A. sojae PGzyme System (PGSYS EXCHANGE)”. Funded by FP7-PEOPLE-2010-IRSES (EU’s Seventh Framework Programme (FP7); SP3-People (Support for training and career development of researchers); Marie Curie International Research Staff Exchange Scheme (IRSES)).|
|2011-2012||“Prototyping (Entwicklung von Nonwoven, Kartuschen und Packtechnik) und Produktentwicklung”. Funded by ZIM (Zentrales Innovationsprogramm Mittelstand / Central Innovation Programme SME, Federal Ministry of Economics and Technology (BMWi), Germany). This project is in co-operation with Chipro GmbH, Bremen, Germany.|
|2011-2012||“Biomass adsorbent interactions during expanded bed adsorption”. Co-operation project with DSM (Company Funded Project), Netherland.|
|2010-2013||“Probing Biomass Interactions in Expanded Bed Adsorption by Atomic Force Microscopy”. Funded by DFG (Deutsche Forschungsgemeinschaft / German Research Foundation, Germany).|
|2009-2010||“Polygalacturonase Systems”, an industrial project devoted to the development of microbial strain(s), processing strategies, and enzyme immobilization methods. Funded by BMBF (Bundesministerium für Bildung und Forschung, Germany).|
|2009-2010||“Research for the benefit of specific Groups (in particular SMEs). Protien electroextraction coupled to direct sorption – a new route for primary recovery of intracellular bioproducts from industrial yeast (Co-Ordinator). Funded by EU-FP7 (EU’s Seventh Framework Programme (FP7)).|
|2008-2009||Research agreement on “Affinity-Process Proteomics”. Funded by Novo Nordisk A/S, Copenhagen, Denmark.|
|2008-2009||“Production and downstream processing of fungal enzyme under conditions close to industrial practice” In co-operation with the Izmir Institute of Technology (Prof. Dr. Canan Tari). Funded by BMBF (Bundesministerium für Bildung und Forschung, Germany).|
|2007-2009||“Resource preserving one-step purification of biopharmaceuticals”. Funded by Bremer Senator für Umwelt, Bau, Verkehr und Europa. In co-operation with ChiPro GmbH.|
|2003-2006||International University Bremen GmbH, Bremen, Germany. Start-up Fund Number 2130-90127.|
|2003-2006||ANPCyT (PICT 2003) 14-13436 “Desarrollo de tecnologia nacional para la sustitucion de importaciones: Peroxidasa y Pectinasas” (Co-Director).|
|2003-2004||“Desarrollo de un proceso contínuo para la simultánea recuperación y purificación de productos naturales: prototipo a nivel laboratorio” (Director). Funded by National Agency for the Promotion of Science and Technology. Buenos Aires, Argentina. R&D Grant NA 136/2003. Industrial partner: Naturis SA.|
|2002-2003||“Downstream processing of low molecular weight compounds” (Director). Funded by National Agency for the Promotion of Science and Technology. Buenos Aires, Argentina. R&D Grant. Industrial partner: Naturis SA.|
|2001-2004||“Downstream processing of biotechnological products: the “meta-integration” concept for fast-track product delivery” (Director). Funded by National Agency for the Promotion of Science and Technology.Buenos Aires, Argentina.|
Areces LB, Bonino MB, Parry MA, Fraile ER, Fernandez HM, Cascone O: Purification and characterization of a milk clotting protease from Mucor bacilliformis. Appl Biochem Biotechnol 1992, 37(3):283-294.
Lahore HMF, Miranda MV, Fraile ER, Bonino MJBD, Cascone O: Partition Behavior and Purification of a Mucor-Bacilliformis Acid Protease in Aqueous 2-Phase Systems. Process Biochem 1995, 30(7):615-621.
Miranda MV, Lahore HMF, Cascone O: Horseradish-Peroxidase Extraction and Purification by Aqueous 2-Phase Partition. Appl Biochem Biotech 1995, 53(2):147-154.
Miranda MV, Lahore HMF, Cascone O: Partition behaviour of thaumatin derivatives in poly(ethyleneglycol)/salt aqueous two-phase systems. Bioseparation 1996, 6(5):315-321.
Fernandez Lahore HM, Gallego Duaigues MV, Cascone O, Fraile ER: Solid state production of a Mucor bacilliformis acid protease. Revista Argentina de microbiologia 1997, 29(1):1-6.
Grasselli M NdCA, Fernández-Lahore HM, Miranda MV, Camperi SA, and Cascone O: Qué hacer con el suero de leche. Ciencia Hoy 1997, 8(43):12-17.
Fernandez-Lahore HM, Fraile ER, Cascone O: Acid protease recovery from a solid-state fermentation system. Journal of Biotechnology 1998, 62(2):83-93.
Miranda MV, Fernandez-Lahore HM, Dobrecky J, Cascone O: The extractive purification of peroxidase from plant raw materials in aqueous two-phase systems. Acta Biotechnol 1998, 18(3):179-188.
Thommes J, Feuser J, Fernandez-Lahore M, Kula MR: The influence of cell adsorbent interactions on protein adsorption in fluidised beds. Abstr Pap Am Chem S 1998, 216:U246-U246.
Fernandez-Lahore HM, Auday RM, Fraile ER, Bonino MBDJ, Pirpignani L, Machalinski C, Cascone O: Purification and characterization of an acid proteinase from mesophilic Mucor sp solid-state cultures. J Pept Res 1999, 53(6):599-605.
Fernandez-Lahore HM, Kleef R, Kula MR, Thommes J: The influence of complex biological feedstock on the fluidization and bed stability in expanded bed adsorption. Biotechnology and Bioengineering 1999,64(4):484-496.
Fernandez-Lahore HM, Geilenkirchen S, Boldt K, Nagel A, Kula MR, Thommes J: The influence of cell adsorbent interactions on protein adsorption in expanded beds. Journal of Chromatography A 2000, 873(2):195-208.
Cabrera R SR, López P, Ferraro G, Cascone O, Fernández-Lahore H M: Protein separation from biological complex mixtures employing continuous liquid-liquid extraction processes (in Spanish). FABICIB 2001, 5:107-118.
del Canizo AAN, Lahore HMF, Miranda MV, Cascone O: Acid protease purification by dye affinity chromatography. Afinidad 2001, 58(493):231-233.
Fernandez-Lahore HM, Lin DQ, Hubbuch JJ, Kula MR, Thommes J: The use of ion-selective electrodes for evaluating residence time distributions in expanded bed adsorption systems. Biotechnol Progr 2001,17(6):1128-1136.
Kijak GH, Camperi SA, Stumpo R, Cascone O, Lahore HMF: Extractive fractionation of equine hyperimmune plasma. Separ Sci Technol 2001, 36(1):59-79.
Lin DQ, Fernandez-Lahore HM, Kula MR, Thommes J: Minimising biomass/adsorbent interactions in expanded bed adsorption processes: a methodological design approach. Bioseparation 2001, 10(1-3):7-19.
Magri ML, Cabrera RB, Miranda MV, Fernandez-Lahore HM, Cascone O: Performance of an aqueous two-phase-based countercurrent chromatographic system for horseradish peroxidase purification. Journal of Separation Science 2003, 26(18):1701-1706.
Saccodossi N, Cabrera RB, Oliver F, Gelmi L, Magglio DG, Fernandez-Lahore HM, Leoni J, Stumpo RR: Chemical extraction and direct adsorptive purification of recombinant human antigen Ro52. Journal of Separation Science 2004, 27(7-8):589-594.
Cabrera RB, Fernandez-Lahore HM: Sorption characteristics and performance of an acid dye on a gel-type weak anion exchanger in a finite bath. J Sci Food Agr 2006, 86(14):2318-2326.
Cabrera R, Femandez-Lahore M: Global screening of protein chromatographic behavior on ion exchangers from a complex cell proteome Towards in silico downstream processing of bioproducts. Journal of Chromatography A 2007, 1161(1-2):41-50.
Cabrera RB, Fernandez-Lahore HM: Primary recovery of acid food colorant. Int J Food Sci Tech 2007,42(11):1315-1326.
Cabrera R, Zhelyazkova P, Galvis L, Fernandez-Lahore M: Tailoring orthogonal proteomic routines to understand protein separation during ion exchange chromatography. Journal of Separation Science 2008, 31(13):2500-2510.
Tari C, Vennapusa RR, Cabrera RB, Fernandez-Lahore M: Colloid deposition experiments as a diagnostic tool for biomass attachment onto bioproduct adsorbent surfaces. J Chem Technol Biot 2008, 83(2):183-191.
Vennapusa R, Hunegnaw SM, Cabrera RB, Fernandez-Lahore M: Assessing adsorbent-biomass interactions during expanded bed adsorption onto ion exchangers utilizing surface energetics. Journal of Chromatography A 2008, 1181(1-2):9-20.
Vennapusa RR, Binner S, Cabrera R, Fernandez-Lahore M: Surface Energetics to Assess Microbial Adhesion onto Fluidized Chromatography Adsorbents. Eng Life Sci 2008, 8(5):530-539.
Ventura AM, Lahore HMF, Smolko EE, Grasselli M: High-speed protein purification by adsorptive cation-exchange hollow-fiber cartridges. J Membrane Sci 2008, 321(2):350-355.
Islam T, Khan RA, Khan MA, Rahman MA, Fernandez-Lahore M, Huque QMI, Islam R: Physico-Mechanical and Degradation Properties of Gamma-Irradiated Biocomposites of Jute Fabric-Reinforced Poly(caprolactone). Polym-Plast Technol 2009, 48(11):1198-1205.
Marcelo Fernández Lahore OA, Rami Reddy Vennapusa, Muhammad Aasim: Expanded Bed Chromatography, Surface Energetics of Biomass Deposition. Wiley Encyclopedia of Industrial Biotechnology 2009.
R.R.Vennapusa MF-L: Electroextraction and rapid isolation of bioproducts from industrial yeast. Europe BIOforum 2009, 13(8-9):14-16.
Vennapusa RR, Aasim M, Cabrera R, Fernandez-Lahore M: Surface Energetics to Assess Biomass Attachment onto Immobilized Metal-ion Chromatography Adsorbents in Expanded Beds. Biotechnol Bioproc E 2009, 14(4):419-428.
Vennapusa RR, Tari C, Cabrera R, Fernandez-Lahore M: Surface energetics to assess biomass attachment onto hydrophobic interaction adsorbents in expanded beds. Biochem Eng J 2009, 43(1):16-26.
Buyukkileci AO, Tari C, Fernandez-Lahore HM, Demir HG, Gogus N: Optimization of Exo-Polygalacturonase Production from Orange Peel by Aspergillus sojae. Journal of Biotechnology 2010, 150:S414-S415.
Vennapusa RR, Aguilar O, Mintong JMB, Helms G, Fritz J, Lahore MF: Biomass-Adsorbent Adhesion Forces as an Useful Indicator of Performance in Expanded Beds. Separ Sci Technol 2010, 45(15):2335-2344.
Vennapusa RR, Fernandez-Lahore M: Effect of chemical additives on biomass deposition onto beaded adsorbents. J Biosci Bioeng 2010, 110(5):564-571.
Yegin S, Fernandez-Lahore M, Guvenc U, Goksungur Y: Production of extracellular aspartic protease in submerged fermentation with Mucor mucedo DSM 809. Afr J Biotechnol 2010, 9(38):6380-6386.
Bibi NS, Gavara PR, Espinosa SLS, Grasselli M, Fernandez-Lahore M: Synthesis and Performance of 3D-Megaporous Structures for Enzyme Immobilization and Protein Capture. Biotechnol Progr 2011,27(5):1329-1338.
Buyukkileci AO, Tari C, Fernandez-Lahore M: Enhanced Production of Exo-Polygalacturonase from Agro-Based Products by Aspergillus Sojae. Bioresources 2011, 6(3):3452-3468.
Helms G, Fernandez-Lahore M, Vennapusa RR, Fritz J: Probing biomass-chromatographic bead interactions by AFM force spectroscopy. Eur Biophys J Biophy 2011, 40:227-228.
Yegin S, Fernandez-Lahore M, Salgado AJG, Guvenc U, Goksungur Y, Tari C: Aspartic proteinases from Mucor spp. in cheese manufacturing. Appl Microbiol Biot 2011, 89(4):949-960.
Aasim M, Bibi NS, Vennapusa RR, Fernandez-Lahore M: Extended DLVO calculations expose the role of the structural nature of the adsorbent beads during chromatography. Journal of Separation Science 2012,35(9):1068-1078.
Bibi NS, Galvis L, Grasselli M, Fernandez-Lahore M: Synthesis and sorption performance of highly specific imprinted particles for the direct recovery of carminic acid. Process Biochem 2012, 47(9):1327-1334.
Boeris V, Balce I, Vennapusa RR, Rodriguez MA, Pico G, Lahore MF: Production, recovery and purification of a recombinant beta-galactosidase by expanded bed anion exchange adsorption. J Chromatogr B 2012,900:32-37.
Demir H, Gogus N, Tari C, Heerd D, Lahore MF: Optimization of the process parameters for the utilization of orange peel to produce polygalacturonase by solid-state fermentation from an Aspergillus sojae mutant strain. Turk J Biol 2012, 36(4):394-404.
Gavara PR, Cabrera R, Vennapusa RR, Grasselli M, Fernandez-Lahore M: Preparation, characterization, and process performance of composite fibrous adsorbents as cation exchangers for high throughput and high capacity bioseparations. J Chromatogr B 2012, 903:14-22.
Heerd D, Yegin S, Tari C, Fernandez-Lahore M: Pectinase enzyme-complex production by Aspergillus spp. in solid-state fermentation: A comparative study. Food Bioprod Process 2012, 90(C2):102-110.
Mikutis G, Karakose H, Jaiswal R, Legresley A, Islam T, Fernandez-Lahore M, Kuhnert N: Phenolic promiscuity in the cell nucleus – epigallocatechingallate (EGCG) and theaflavin-3,3′-digallate from green and black tea bind to model cell nuclear structures including histone proteins, double stranded DNA and telomeric quadruplex DNA. Food Funct 2012.
Nour HF, Islam T, Fernandez-Lahore M, Kuhnert N: Probing the dynamic reversibility and generation of dynamic combinatorial libraries in the presence of bacterial model oligopeptides as templating guests of tetra-carbohydrazide macrocycles using electrospray mass spectrometry. Rapid Commun Mass Spectrom 2012, 26(24):2865-2876.
Yegin S, Fernandez-Lahore M: A Thermolabile Aspartic Proteinase from Mucor mucedo DSM 809: Gene Identification, Cloning, and Functional Expression in Pichia pastoris. Mol Biotechnol 2012.
Yegin S, Goksungur Y, Fernandez-Lahore M: Purification, structural characterization, and technological properties of an aspartyl proteinase from submerged cultures of Mucor mucedo DSM 809. Food Chem 2012, 133(4):1312-1319.
Bibi NS, Singh NK, Dsouza RN, Aasim M, Fernandez-Lahore M: Synthesis and performance of megaporous immobilized metal-ion affinity cryogels for recombinant protein capture and purification. J Chromatogr A 2013, 1272:145-149.
Certificate of Residency Program, Clin. Chem. Microbiol., BUE City Health System (1989)