Search anything and hit enter
  • Teams
  • Members
  • Projects
  • Events
  • Calls
  • Jobs
  • publications
  • Software
  • Tools
  • Network
  • Equipment

A little guide for advanced search:

  • Tip 1. You can use quotes "" to search for an exact expression.
    Example: "cell division"
  • Tip 2. You can use + symbol to restrict results containing all words.
    Example: +cell +stem
  • Tip 3. You can use + and - symbols to force inclusion or exclusion of specific words.
    Example: +cell -stem
e.g. searching for members in projects tagged cancer
Search for
Count
IN
OUT
Content 1
  • member
  • team
  • department
  • center
  • program_project
  • nrc
  • whocc
  • project
  • software
  • tool
  • patent
  • Administrative Staff
  • Assistant Professor
  • Associate Professor
  • Clinical Research Assistant
  • Clinical Research Nurse
  • Clinician Researcher
  • Department Manager
  • Dual-education Student
  • Full Professor
  • Honorary Professor
  • Lab assistant
  • Master Student
  • Non-permanent Researcher
  • Nursing Staff
  • Permanent Researcher
  • Pharmacist
  • PhD Student
  • Physician
  • Post-doc
  • Prize
  • Project Manager
  • Research Associate
  • Research Engineer
  • Retired scientist
  • Technician
  • Undergraduate Student
  • Veterinary
  • Visiting Scientist
  • Deputy Director of Center
  • Deputy Director of Department
  • Deputy Director of National Reference Center
  • Deputy Head of Facility
  • Director of Center
  • Director of Department
  • Director of Institute
  • Director of National Reference Center
  • Group Leader
  • Head of Facility
  • Head of Operations
  • Head of Structure
  • Honorary President of the Departement
  • Labex Coordinator
Content 2
  • member
  • team
  • department
  • center
  • program_project
  • nrc
  • whocc
  • project
  • software
  • tool
  • patent
  • Administrative Staff
  • Assistant Professor
  • Associate Professor
  • Clinical Research Assistant
  • Clinical Research Nurse
  • Clinician Researcher
  • Department Manager
  • Dual-education Student
  • Full Professor
  • Honorary Professor
  • Lab assistant
  • Master Student
  • Non-permanent Researcher
  • Nursing Staff
  • Permanent Researcher
  • Pharmacist
  • PhD Student
  • Physician
  • Post-doc
  • Prize
  • Project Manager
  • Research Associate
  • Research Engineer
  • Retired scientist
  • Technician
  • Undergraduate Student
  • Veterinary
  • Visiting Scientist
  • Deputy Director of Center
  • Deputy Director of Department
  • Deputy Director of National Reference Center
  • Deputy Head of Facility
  • Director of Center
  • Director of Department
  • Director of Institute
  • Director of National Reference Center
  • Group Leader
  • Head of Facility
  • Head of Operations
  • Head of Structure
  • Honorary President of the Departement
  • Labex Coordinator
Search
Go back
Scroll to top
Share

About


Welcome to the laboratory “Membrane Biochemistry and Transport”!

Have you ever wondered how human cells get rid of waste? If yes, we have some answers and exciting research projects that aim to reveal the fundamental principles of autophagy, the most versatile cellular recycling pathway.

What is autophagy?

Autophagy is a fascinating cellular degradation pathway that selects cytoplasmic material, sequesters it in autophagosomes and transports it to lysosomes for degradation. Autophagic cargo, including organelles, protein aggregates, ribosomes and multienzyme complexes, is captured by a membrane cisterna, termed phagophore. The membrane expands around its cargo to engulf it entirely and sealing of the membrane gives rise to an autophagosome, which is a “transport container” that delivers its content to lysosomes.

Why do we study autophagy?

The importance of autophagy for the homeostasis and stress resistance of human cells cannot be appreciated enough. Autophagy takes a central position in cellular catabolism and is interconnected with many other cellular pathways. Reduced autophagic activity or dysfunctions are contributing to the onset of many human diseases, including cancer, neurodegeneration, metabolic and immune diseases. Such a decline of autophagy occurs during aging, leading to a higher prevalence of neurogenerative diseases and cancer in the older population. A directed and precise manipulation of the autophagic activity offers so far unexplored options to treat those diseases, notably neurodegenerative diseases for which no efficient treatment exists.

How do we study autophagy?

We are combining two different approaches to investigate autophagy. The first aims to reconstitute the formation of autophagosomes in the test tube from purified components. We use model membranes which are assembled from synthetic lipids and purified proteins, which we express recombinantly using E.coli, insect, or human cells.

Reconstitution of autophagy in the test tube. Purified recombinant proteins are incubated with model membranes to generate artificial autophagosomes. Electron micrographes show membrane cups on model membranes at different stages during their formation.


The second approach combines cell biology, biochemistry, biophysical analysis and structural studies in cultured cells. Here, we uncouple parts of the autophagy machinery from the pathway by redirecting them to other membranes, for example the plasma membrane or organellar membranes. This “in vivo” reconstitution approach allows us to study the activity of components of the autophagy machinery and their molecular function independently of canonical autophagy. Therefore, we express fluorescent labeled proteins and study their interaction on membranes by e.g. fluorescence lifetime imaging. The hallmark of autophagy is the formation of phagophores and autophagosomes, which depends on massive remodeling of cellular membranes. In order to correlate protein function with such membrane deformations, we apply electron microscopy techniques including correlative light electron microscopy, focused ion beam – scanning electron microscopy and cryo-electron tomography.

Autophagy and neurodegeneration

We recently identified a specialized autophagy pathway that degrades protein aggregates in neural cells. We found that autophagosomes that transport protein aggregates to lysosomes are decorated with LC3C, a small ubiquitin like protein which belongs to the ATG8 protein family. LC3C is covalently attached to lipids of the phagophore membrane and provides identity to such autophagosomes. The destination of LC3C labeled autophagosomes is defined by TECPR1, a protein that is found on a subtype of lysosomes that contain the lipid PtdIns(4)P in their membrane. TECPR1 selectively interacts with LC3C to recruit protein aggregate containing autophagosomes. Targeting TECPR1 to endosomes leads to a missorting of LC3C autophagosomes, which are no longer delivered to lysosomes for degradation but accumulate at endosomes instead.

Left: Neural cells of healthy brains degrade protein aggregates by autophagy. TECPR1 (green) is expressed in these cells and ubiquitinated protein aggregates (red), are not detected.
Right: The activity of autophagy decline with age, and in some older people, protein aggregates accumulate in neurons of the brain, leading to neurodegeneration.

We found that impaired autophagy, which entails an accumulation of protein aggregates, can be reverted. If protein levels of TECPR1 in neural cells are restored, the autophagic activity in these cells is augmented. This leads to an enhanced clearance of protein aggregates, protecting neural cells from cytotoxicity and cell death. Many neurodegenerative diseases are caused by an accumulation of proteins including alpha-synuclein and Tau in the case of Alzheimer’s and Parkinson’s diseases. Our findings demonstrate that neurodegeneration can be treated by selectively enhancing TECPR1 levels.

If you want to lean more about this project, you can click on this link: Paper “TECPR1 promotes aggrephagy by direct recruitment of LC3C autophagosomes to lysosomes”

Nonselective autophagy and stress response

Autophagy does not only degrade cytoplasmic waste, it also degrades bulk cytoplasm in cells that encounter cytotoxic stress or in response to starvation. But there is a major difference between selective autophagy of cytoplasmic cargo and nonselective autophagy of bulk cytoplasm. In selective autophagy, the membrane wraps around cargo. The shape of the membrane is thus defined by the shape of cargo. In nonselective autophagy, bulk cytoplasm, which is a viscous solution, needs to be captured by a membrane that behaves like a two-dimensional liquid. Thus, nonselective autophagy requires that phagophores are shaped into free standing membrane cups, which expand without templating cargo to enclose portions of cytoplasm. How this can be achieved, remained a longstanding question. We recently found that another member of the ATG8 protein family, LC3B and its E3-ligase complex, which catalyzes the conjugation of LC3B to membranes, play a key role in the process. Both assemble into two-dimensional scaffolds that deform flat donor membranes into membrane cups. By reconstituting this process on model membrane in vitro and at the plasma membrane of cells, we revealed unprecedented insights into the molecular mechanism of this process and identified a subunit of the E3 ligase complex, ATG16L1, as a key driver of cup formation.

If you are interested to lean more about this project, you can read the full story at: Preprint “Phagophore formation by the autophagy conjugation machinery”

Social Activities 2019:   Birthday Party for Thomas

Celebration of Thomas’ Birthday, Terrasse of the Francois Jacob Building at the Institut Pasteur

PhD celebration Peter

Celebration after Peter’s PhD defence at the Max Planck Institute of Biochemistry in Martinsried (Germany)

2018:   World Soccer Championships 2018

Football WM 2018 – Quarter Final France – Uruguay

Birthday Cake for Thomas

Thomas’ Birthday

Birthday Cake for Jagan

Jagan’s Birthday

Birthday Cake for Peter

Peter’s Birthday

2017:   Christmas Party

Fête de Noël 2017

Former Members

2000
2000
Name
Position
2017
2019
Peter Mayrhofer
PhD Student
2017
2020
Satish Moparthi
Post Doc Research Assistant
2021
2021
Gwendal Guerin
Engineere Internship
2016
2017
Anthony Yasmann
PhD Student
2019
2020
Mériem Khalfaoui
Work/Study training program
2019
2021
Charlotte Nugues
Post Doc Research Assistant
2017
2022
Jagan Mohan H.D.
Post Doc Research Assistant
2020
2022
Saloni Patel
Post Doc Research Assistant
2022
2022
Tolgahan Suat Sezen
Master 1 trainee
2021
2021
Tak Wang Terence Lee
PhD from HKU-Pasteur Research pole Fellowship programm

Transversal Project

Equipments

Microscope confocal inverted FLIM • Leica • SP8

Inverted microscope fully motorized, equipped with a laser scanning confocal head and a TIRF unit. It allows the acquisition in spectral mode, multi-positions,  multi-mosaics. Features : Available light sources 405 nm 50 mW 488 […]

Fundings

Featured publications

Download

Becoming part of our team

We are a very dynamic, open, interactive, and multidisciplinary research laboratory. We meet the challenges that we are facing in our daily research by using cutting edge techniques including cell culture, fluorescent microscopy, genome editing, recombinant protein expression and purification, reconstitution reactions with model membranes, and structural biology.

Are you worrying that this sounds too much for you?

Don’t worry! Our supportive team members are taking care that you get to handle these techniques. Stèphane has a long standing expertise in cell biology and in handling neural cells as well as pluripotent and neural stem cells. Christine is an expert in protein production, electron microscopy and correlative light electron microscopy. Jagan has setup in vitro reconstitution reactions and knows how to handle model membranes. All members of our team are experienced cell biologists and biochemists. Our combinatorial approach is unique as it allows us to address the most difficult and challenging questions in fundamental biology.

Become part of our team

We are always looking for new team members who are interested in our research. We encourage highly motivated and talented PhD-students and Postdocs who are experienced in either biophysical / biochemical methods or cell biology to apply. The complementary training in our laboratory will provide you with the opportunity to work at the interface of cell biology, biochemistry and biophysics! Applicants should send a detailed letter explaining their motivation, their previous experience and how they want to contribute to our research along with CV and contact information for three referees to: thomas.wollert@pasteur.fr

Contact

Centre François Jacob, 3er étage, Room 26-03-07b Institut Pasteur 75015 Paris France Email:thomas.wollert@pasteur.fr Phone: +33 (0) 140 61 31 46 Fax:+33 (0) 140 61 31 48