Joakim Larsson's group

Group members
Lina Gunnarsson, Filip Cuklev, Dr Jeff Brown, Eva Albertsson, Andreas Kullgren, Dr Erik Kristiansson, Dr Noomi Asker, Birgitta Weijdegård, Caroline Rutgersson, Anna Bylander, Anders Janzon, Anna Johnning, Ida Nilsson and Dr Joakim Larsson
 

Resistance in environmental bacteria evolving under extreme antibiotic selection pressure – characterization of the resistance genes we may face tomorrow
 

PhD student project 2010-2013 co-financed by the Sahlgrenska Academy

The heavy use of antibiotics in human and veterinary medicine is a major driving force behind the development of multi-resistant bacteria. Antibiotics find their way to the environment through excretion and via effluents from manufacturers. This promotes the development of resistant bacteria, which can serve as a recruitment pool for resistance genes to human pathogens through horizontal gene transfer.

The aim of this project is to assess risks of extreme antibiotic contamination in the environment. Environmental samples from areas heavily contaminated with antibiotics will be analyzed using large-scale gene-sequencing techniques, and resistant bacteria and their resistance factors investigated. Meta-genomic analysis will provide culture-independent information on a community level and whole-genome sequencing will identify important genetic alterations. Experimental work will be undertaken to identify novel resistance factors and the presence of transfer mechanisms. A clinical study is proposed to establish links between environmental exposure to antibiotics and resistance factors in the human microbiome.

The PhD position will be formally announced at the webpage of University of Gothenburg at the end of October (www.gu.se). Estimated start is January, 2010.

Pharmaceutical pollution – antibiotic resistance development and mode-of-action based test strategies
 

Senior scientist position 3+3 years from 2009 within the field of Translational Pharmacology including startup-grant from the Swedish Research Council (Medicine).

This grant covers research on several aspects on environmental effects of pharmaceuticals where there currently are major knowledge gaps. My group will focus on three areas:

1. assess risks (including resistance development) associated with the extaordinary large releases of antibiotics and other pharmaceuticals from bulk drug producers in India
2. identify drugs likely to cause environmental effects and contribute to a scientifically founded framework for mode-of-action based environmental risk assessments of human pharmaceuticals
3. evaluate effluent treatment technologies to reduce the environmental impact of pharmaceuticals
   
   

    

Microbial diversity and development of antibiotic resistance associated with industrial wastewater treatment
 

Swedish Research Link programme funded 2009-2011 by SIDA.

The Swedish Research Links programme from SIDA aims to stimulate research cooperation between researchers in Sweden and researchers in Asia, the Middle East and North Africa (MENA) region and South Africa. One important focus is to stimulate the mobility for the involved scientists. Within this collaborative project between the University of Gothenburg and Indian scientists, we intend to analyze the impact of extraordinary high levels of antibiotic pollution from pharmaceutical manufacturing near Hyderabad, India, on bacterial diversity and the development of antibiotic resistance. We will also study the potential impact on the emergence of antibiotic-resistant bacterial pathogens as well as the genetic background to their resistance. This research will provide insights into the relationships between selection processes due to antibiotic pollution and subsequent development of resistance.
 

Consumption of inexpensive medicines – increased risks for resistance development and environmental effects?
 

PhD-student project funded by the Research School for Environment and Health in Göteborg 2008-2012.

Pharmaceuticals are thought to reach the aquatic environment primarily via sewage effluents, where for example estrogens can feminize fish. Antibiotics in normal treated sewage effluents are not believed to cause resistance or affect microbial diversity. However, we recently showed that treated effluent from 90 production sites in India contains extremely high, toxic levels of antibiotics, with ciprofloxacin up to 1 million times the levels normally found in sewage effluents. We will start to address the environmental impact of the release of pharmaceuticals at this centre for the global bulk-drug market. This will also include the impact on species diversity and resistance development of bacterial communities. The project will also address different possibilities of how the situation can be improved. We believe the project will provide new knowledge on antibiotic pollution and the subsequent development of resistance, of urgent importance for improving regulatory standards for production units world-wide. The project will be performed in collaboration with several other research groups, both in Sweden and India.
 

Endocrine disruption of non-genomic progesterone signalling – consequences for gamete transport and sex ratios

Research program funded by the Swedish Council for Environment, Agricultural Sciences and Spatial Planning (FORMAS) 2008-2010 to Joakim Larsson.

The aim of this project is to investigate how progesterone and various endocrine disrupters affect membrane progesterone receptor expression, oviductal ciliary activity, gamete transport and male to female ratios among the offspring in a mouse model. Within the project, the development and application of ciliary activity analysis together with Dr Mattias Goksör (Physics, GU) is particularly important. We believe our research will contribute both to our understanding of the gamete transport and the physiological control of sex in mammals as well as to better understand the interference by pollutants in these processes. In the future, this research could potentially pave the way for drugs or other treatments to reduce the risks for ectopic pregnancies in women.
 

BALCOFISH - Integration of pollutant gene responses and fish ecology in Baltic coastal fisheries and management
 

Research project funded by the European BONUS program 2008-2012

The overall objective of the BALCOFISH project is to provide science-based input to foster the development of appropriate measures in the management of the Baltic Sea environment to protect it against anthropogenic chemical pollution. For this purpose it is important to unravel causal links between the current pollution situation and effects observed in the field. To establish such links we will develop novel toxicogenomics approaches and integrate these with existing early effects biomarkers. These responses will be anchored to effects relevant to the sustainability of coastal fish populations of the Baltic Sea, such as impaired reproduction. We will systematically test strengths of evidences supporting causal linkages between contaminants and effects on Baltic fish by using a formal weight-of-evidence approach. The BALCOFISH project is coordinated by Gothenburg University (Lars Förlin, Zoology) and involves partners from the Sahlgrenska Academy (our group), University of Aarhus (Denmark), Swedish Board of Fisheries, Institute for Applied Ecology (Germany) Department of Biomedical Sciences and Veterinary Public Health, Swedish University of Agricultural Sciences (Sweden) and the Swedish Museum of Natural History, Sweden. In total 16 BONUS projects were funded in June 2008 (out of 149 application), with a total budget of 22 Million Euro.
 

MistraPharma - Identification and reduction of environmental risk caused by the use of human pharmaceuticals.

 

Research program supported by the Swedish Foundation for Strategic Environmental Research (MISTRA) 2008-2011 with 44.2 MSEK.

This research program will take a comprehensive approach for prioritizing environmental research on the majority of the human drugs used in Sweden in order to facilitate possible mitigations. Bioconcentration into fish blood plasma will be assessed for about 100 substances using fish exposed to various sewage effluents. For the drugs showing the highest fish blood plasma levels in comparison with human therapeutic levels, comprehensive biological effect studies will be performed. Other strategies for prioritization will be applied as well. The effect studies include both directed, mechanism-of action-based analyses as well as different exploratory approaches using for example microarrays and histology. Rainbow trout and Daphnia will be the primary test models. The efficacy of a range of different treatment technologies will be evaluated with particular respect to the most highly ranked drugs. Different test strategies will be evaluated which will be used to improve existing risk assessment procedures. MistraPharma has been developed and will be performed in close collaboration with the water treatment companies, the health care sector, representatives for industries, environmental agencies and the Medical Products Agency.

Involved partners are in addition to our research group at the Sahlgrenska Academy at Göteborg University: the Royal Institute of Technology, Uppsala University, Stockholm University, Umeå University, LundUniversity/Denmarks Technical University and Kemi&Miljö. The program director will be Dr Christina Rudén at the Royal Institute of Technology.

Our research on environmental effects of pharmaceuticals is one example of how Göteborg University and the Sahlgrenska Academy work proactively with environmental issues. Sustainable development is emphasized in many courses for students as well. Click on this link to view a short presentation (in Swedish).
 

Multi-Endpoint Microarray Analyses in Biological Effect Monitoring of Wild Fish Populations
 

Project funded by FORMAS to Lars Förlin and Joakim Larsson 2007-2009

In this project we will merge genomics and ecotoxicology (ecotoxicogenomics) to explore the utility in biomonitoring of wild fish populations. Specifically we plan to: 1) develop microarrays to assess environmental effects of pollutants in wild fish species 2) to use these to link molecular responses to pollutants with the individual reproductive performance of the viviparous eelpout in its natural environment 3) to establish a cDNA biobank from wild eelpout sampled yearly, allowing the possibililty to back-track the progression of upcoming wide-spread environmental disturbances in the future 4) to monitor freshwater fish populations (roach) to investigate biological responses to chemicals in sewage effluents (including pharmceuticals). With the aid of an advanced utra-flexible microarray robot (Geniom) we can in principal perform microarrays with any species where sequence information is available. We are currently hampered by the lack of mRNA sequence data for eelpout. We will therefore begin by constructing and partially sequencing a cDNA liver library for the eelpout. Our approach to study wild fish population in their natural environment makes it possible to identify difficulties and possibilities related to studies of complex mixtures in which chemicals act in concert.
 

Ecotoxicology – from gene to ocean
 

Interdisciplinary research platform (Joakim Larsson co-applicant together with L Förlin, H Blanck, G Dave and M Celander) funded by the Science faculty at Göteborg University 2007 – 2010.

In this platform we intend use a set of genome-wide approaches to identify responses and mechanisms of action of individual chemicals and their mixtures. The platform encompasses different subprojects dealing with ecotoxicological effects of marine antifouling paints and pharmaceuticals to mention a couple of examples. We will extend our approach from single species and single chemicals to complex, contaminated ecosystems. The platform brings together scientists from complementing disciplines in molecular genetics, cell biology, physiological, organismic and community ecotoxicology and mode of action research. This interdisciplinary team will integrate current individual research efforts in genomics and ecotoxicology at Göteborg University. Or vision is to consolidate, renew and strengthen ongoing research, as well as providing the critical mass for future research applications on a national as well as international level.
 

Metabolic processes underlying seasonal growth patterns in fish
 

Research project funded by the Science Faculty at Göteborg University within the larger GRIP-platform (Göteborg Research on Integrative Physiology: http://www.grip.science.gu.se/ ). 2006-2009. The project is jointly coordinated between departments of Zoophysiology (Elisabeth Jönsson, Thrandur Björnsson), Zooecology (Jörgen Johnsson) and the Sahlgrenska Academy (Joakim Larsson)

The project objective is to improve the understanding of the metabolic processes underlying seasonal growth patterns in fish, and link this to ecological questions. Focus will be on the influence of food availability, temperature, and population density on the endocrine regulation of growth patterns and associated metabolic processes in whole animals, in the lab and field. The research aim to advance the understanding of physiological mechanisms behind seasonal adaptations, thus increasing our ability to predict consequences of climatic changes on fish populations.