Research overview

In the Olsen laboratory, we have an interest in ageing and age-related neurodegenerative diseases - in particular the underlying molecular mechanisms. We believe that these mechanisms hold the key to prevent and treat age-related diseases. We are looking for novel genes and compounds that increase lifespan and delay the onset of disease. We also have a growing interest in the microbiome and probiotic bacteria and their effect on longevity and stress resistance e.g pathogenic bacteria. Finally, we are studying the role of the molecular motor dynein in programmed cell death. For most of our studies, we are using the soil nematode Caenorhabditis elegans.

Why use a nematode to study human biology and diseases?

C. elegans is a small eukaryotic multicellular soil nematode. It is a poplar genetic model organism used worldwide to study complex biological processes such as development, neurobiology and aging.

Over the years sophisticated genetic tools have been developed including mutagenesis protocols, transgenics, RNA interference, GFP markers and CRISPR/Cas9 genome editing. Several of these epic studies have been rewarded with Nobel prizes but they have also provided invaluable genetic tools to the growing community of researchers using C. elegans as model.

From a human point of view C. elegans is a very attractive model because at the genome level there is a high degree of conservation between C. elegans and humans. Simply put, the same genes are controlling the same biological processes in the two species and hence we can use the much simpler nematode to study gene functions. In addition, numerous transgenic models of human diseases have been generated allowing us to search for interventions and knowledge using the powerful genetic toolbox in C. elegans.

Ageing and age-related diseases

With more and more people reaching older ages, understanding ways of securing healthy, active and self-assisted living during old ages becomes more and more urgent. Not simply for the benefit of the aging individual but also to keep the cost associated with care of the elderly at a manageable level. To achieve this we need to improve our understanding of the molecular processes involved with the ageing process. To this end, simple model organisms have proven themselves indispensable.

C. elegans has a relatively short mean lifespan of approximately 3 weeks, which makes it attractive for longevity studies. Single gene mutations can dramatically increase their lifespan. Some special alleles can even increase lifespan more than 10 fold. Interestingly, most mutations that increase longevity also delay the onset of disease in models for age related diseases such as Alzheimer’s and Parkinson’s disease. Therefore, an attractive hypothesis is that delaying the ageing process may be a way of delaying/preventing the onset of age related diseases.

C. elegans hermaphrodites have 302 neurons, considerably simpler than the ~100,000,000,000 found in humans. We are particularly interested in the dopaminergic neurons as these are the ones affected in Parkinson’s disease. There are only 8 of these in C. elegans allowing us to study neurodegeneration at the single cell level.

Microbiomes and probiotics

WHO predicts that lack of effective antibiotics due to antimicrobial resistance is the major current threat to global human health and will claim more human lives than cancer by 2030. Antimicrobial resistance is a direct consequence of massive use of antibiotics. Thus, there is an urgent need for basic research and innovation to reduce the need for antibiotics.  Similar to humans, the C. elegans intestine becomes colonized with bacteria and it is becoming increasingly clear that this microbiome influences health. Beneficial bacteria in the microbiome are called probiotic (meaning “for life”). Shaping the microbiome towards probiotic bacteria is one way of reducing the use of antibiotics.

The natural food source of C. elegans is bacteria. Hence, C. elegans is well suited for studying the beneficial effects of probiotic bacteria and the role of the microbiome.

In collaboration with DuPont, SSI, and Aarhus University, we have isolated a number of new probiotic bacteria that significantly increase lifespan and offer protection against pathogenic bacteria such as methicillin resistant staphylococcus aureus (MRSA) and E.coli ETEC infections. We are currently uncovering their mechanism of action.

The molecular motor dynein and its role in apoptosis

A number of cargo transport systems are operational inside our cells making sure that the right molecules reach the right place at the right time. One the molecular motors transporting cargo is the Dynein protein complex. We have shown that Dynein plays a regulatory role in the process of programmed cell death (apoptosis) (REF3). We are currently investigating how a single motor manages so many different cargoes.

Student projects can include the following techniques in the Olsen lab:

• Classical genetic screens
• CRISPR/Cas9 genome editing
• Epistasis analysis
• Spinning disk confocal microscopy
• Fluorescence microscopy
• COPAS worm sorting
• Infection assays
• Microbiome analysis – 16S and FISH
• Metabolomics (NMR)
• Proteomics (MS)
• PCR and qPCR
• Western blotting